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Valproic acid 

Inducer Abbreviation: VPA
Model Subtype: Chemical
Model Species:Mus musculus
External Link:        
Statistics Box:
No of Reports: 18
No of Models: 36



Model Summary

Prenatal exposure to valproic acid is linked to ASD in humans. In mice, prenatal VPA exposure results in core endophenotypes associated with ASD: deficits in social behaviors, increased repetitive behaviors and abnormal communication behavior.

Human Clinical Evidence Koch S , et al. 1996


Evidence for malformations and cerebral dysfunction after exposure to drug during pregnancy

Exposure

Exposure to drug in utero after consumption by pregnant mother

Mode of Action

Unknown

Usage

VPA is used as an anticonvulsant for certain types of seizures; Treat mania in patients with bipolar; Prevent migraine headaches

References

Type
Title
Author, Year
Primary
Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism.
Additional
Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism.
Additional
Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder.
Additional
Nonexploratory movement and behavioral alterations in a thalidomide or valproic acid-induced autism model rat.
Additional
Modeling environmental risk factors of autism in mice induces IBD-related gut microbial dysbiosis and hyperserotonemia.
Additional
A new neurobehavioral model of autism in mice: pre- and postnatal exposure to sodium valproate.
Additional
Beneficial Effects of Co-Ultramicronized Palmitoylethanolamide/Luteolin in a Mouse Model of Autism and in a Case Report of Autism.
Additional
Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid.
Additional
mS-11, a mimetic of the mSin3-binding helix in NRSF, ameliorates social interaction deficits in a prenatal valproic acid-induced autism mouse model.
Additional
Prenatal exposure to valproic acid leads to reduced expression of synaptic adhesion molecule neuroligin 3 in mice.
Additional
Abnormal Development of the Earliest Cortical Circuits in a Mouse Model of Autism Spectrum Disorder.
Additional
Increased monoamine concentration in the brain and blood of fetal thalidomide- and valproic acid-exposed rat: putative animal models for autism.
Additional
Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-i...
Additional
The Liver X Receptor Agonist TO901317 Ameliorates Behavioral Deficits in Two Mouse Models of Autism.
Additional
mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism.
Additional
Oxytocin improves animal behaviors and ameliorates oxidative stress and inflammation in autistic mice.
Additional
VPA-induced apoptosis and behavioral deficits in neonatal mice.
Additional
The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

M_VPA_1_IN_C

Construct Definition: Administration of VPA on E12 to E17.
Administration Dose: 200 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: E12-E17
Strain of Origin: BALB/c
Model Source: Taconic

M_VPA_2_IN_C

Construct Definition: Administration of VPA on E11 in 1.5 g peanut butter.
Administration Dose: 800 mg/kg
Administration Route: Dietary
Administration Age: E11
Strain of Origin: HS (interbred C57, DBA, Swiss and CF-1)
Model Source:

M_VPA_3_IN_C

Construct Definition: Administration of VPA on E13.
Administration Dose: 600 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: E13
Strain of Origin: BALB/c
Model Source: Taconic

M_VPA_4_IN_C

Construct Definition: Administration of VPA on P14 to male mice.
Administration Dose: 200 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: P14
Strain of Origin: BALB/c
Model Source: Taconic

M_VPA_5_IN_C

Construct Definition: Administration of VPA on P14 to male mice.
Administration Dose: 400 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: P14
Strain of Origin: BALB/c
Model Source: Taconic

M_VPA_6_IN_C

Construct Definition: Administration of VPA on P14 to male mice.
Administration Dose: 50 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: P14
Strain of Origin: BALB/c
Model Source: Taconic

M_VPA_7_IN_C

Construct Definition: Administration of VPA on P14.
Administration Dose: 400 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: P14
Strain of Origin: BALB/c
Model Source:

M_VPA_8_IN_C

Construct Definition: Administration of VPA on E13.
Administration Dose: 600 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: E13
Strain of Origin: C57BL/6Hsd
Model Source: Harlan

M_VPA_10_IN_C

Construct Definition: Administration of VPA on E9.
Administration Dose: 500 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E9
Strain of Origin: ICR
Model Source: Japan SLC Inc.

M_VPA_11_IN_C

Construct Definition: Administration of VPA on E14.5.
Administration Dose: 500 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E14.5
Strain of Origin: ICR
Model Source: Japan SLC Inc.

M_VPA_9_IN_C

Construct Definition: Administration of VPA on E12.5.
Administration Dose: 500 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: ICR
Model Source: Japan SLC Inc.

M_VPA_12_IN_C

Construct Definition: Administration of VPA on E12.5.
Administration Dose: 600 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: Swiss Albino
Model Source:

M_VPA_19_IN_C

Construct Definition: C57/BL6 male mice were injected subcutaneously with saline or sodium valproate (VPA, 400 mg/kg) on postnatal day 14 (P14).
Administration Dose: 400 mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: P14
Strain of Origin: C57/BL6
Model Source: PMID 27701827

M_VPA_13_IN_C

Construct Definition: Administration of VPA. In a transgenerational study the offspring exposed directly to VPA during fetal development are G1.
Administration Dose: 300mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: E10
Strain of Origin: ICR
Model Source: Orient Bio Inc.

M_VPA_14_IN_C_G2

Construct Definition: Second generation (G2) of mice bred by mating the first generation (designated G1) male offspring directly exposed to VPA during embryonic development and nave adult females. These mice are used to study the transgenerational effects (epigenetic, behavioral) of exposure to VPA (without re-exposure to the chemical).
Administration Dose: 300mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: Transgenerational
Strain of Origin: ICR
Model Source: Orient Bio Inc.

M_VPA_15_IN_C_G3

Construct Definition: Third generation (G3) of mice bred by mating the second generation (designated G2) male offspring to nave adult females. These mice are used to study the transgenerational effects (epigenetic, behavioral) of exposure to VPA (without re-exposure to the chemical).
Administration Dose: 300mg/kg
Administration Route: Subcutaneous (s.c.)
Administration Age: Transgenerational
Strain of Origin: ICR
Model Source: Orient Bio Inc.

M_VPA_16_IN_C

Construct Definition: Administration of VPA on E12.
Administration Dose: 500 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12
Strain of Origin: CD1
Model Source: Charles River

M_VPA_17_IN_C

Construct Definition: Administration of VPA on E12.
Administration Dose: 360 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12
Strain of Origin: CD1
Model Source: Charles River

M_VPA_18_IN_C

Construct Definition: At embryonic day 12.5 pregnant dams were intraperitoneally injected with valproic acid (VPA) (500 mg/kg; Sigma-Aldrich, USA), or equivalent amount of saline.
Administration Dose: 500 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6
Model Source: Japan SLC, Inc.

M_VPA_20_IN_C

Construct Definition: Male offsprings of C57Bl/6J females injected with VPA (600mg/kg; ip) at E12.5.
Administration Dose: 600 mg/kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: E12.5
Strain of Origin: C57BL/6J
Model Source: Huafukang Bioscience (Beijing, China)

M_VPA_21_IN_C

Construct Definition: Administration of VPA on E12.5.
Administration Dose: 500 mg/kg
Administration Route: intraperitoneal (i.p.)
Administration Age:
Strain of Origin: ICR (CD1)
Model Source: Japan SLC Inc. (Hamamatsu, Japan)

M_VPA_22_IN_C

Construct Definition: Administration of VPA on P14 in C57Bl/6 male pups at 400mg/kg. Vehicle injected C57Bl6 mice were used as controls; similar to M_VPA_5_IN_C.
Administration Dose: 400 mg/Kg
Administration Route: Intraperitoneal (i.p.)
Administration Age: P14
Strain of Origin: C57BL/6
Model Source: Third Military Medical University (Nanjing, China)

M_VPA_1_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Negative geotaxis 1
  Abnormal
Description:  Abnormal deficits in negative geotaxis demonstrated by longer latency
Exp Paradigm:  Negative geotropism measured by hanging wire test
  Wire hang test
  P6-P14
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_2_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Gene expression 1
  Decreased
Description:  Decreased expression of NLGN3 mRNA in hippocampal regions and somatosensory cortex S1
Exp Paradigm:  Nlgn3 Gene Expression
  In situ hybridization (ish)
  8.5 weeks
Gene expression1
 No change
 In situ hybridization (ish)
 8.5 weeks
Gene expression1
 No change
 In situ hybridization (ish)
 8.5 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Motor phenotype ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_3_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity 1
  Increased
Description:  Increased locomotor activity counts
Exp Paradigm:  Open field test
  Open field test
  Unreported
  Righting response 1
  Decreased
Description:  Decreased mid-air righting reponse
Exp Paradigm:  Female mice: Measure of time taken by animal to correct itself while holding mouse in mid air
  Righting reflex test
  P13-P19
  Size/growth 1
  Increased
Description:  Increased body weight
Exp Paradigm:  General observations
  General observations
  P5-P26
  Spatial reference memory 1
  Decreased
Description:  Decreased spatial reference memory indicated by impaired water maze performance
Exp Paradigm:  Morris Water Maze Task
  Morris water maze test
  P20-P26
Grip strength1
 No change
 Wire hang test
 P13-P19
Motor coordination and balance1
 No change
 Balance beam test
 P20-P26
Negative geotaxis1
 No change
 Wire hang test
 P6-P14
Righting response1
 No change
 Righting reflex test
 P5-P6
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_4_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Righting response 1
  Decreased
Description:  Decreased mid-air righting reponse
Exp Paradigm:  Measure of time taken by animal to correct itself while holding mouse in mid air
  Righting reflex test
  P13-P19
  General locomotor activity 1
  Increased
Description:  Increased locomotor activity counts
Exp Paradigm:  Open field test
  Open field test
  3 weeks
Spatial reference memory1
 No change
 Morris water maze test
 P20-P26
Grip strength1
 No change
 Wire hang test
 P13-P19
Motor coordination and balance1
 No change
 Balance beam test
 3 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_5_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Righting response 1
  Decreased
Description:  Decreased mid-air righting reponse
Exp Paradigm:  Measure of time taken by animal to correct itself while holding mouse in mid air
  Righting reflex test
  P13-P19
  Negative geotaxis 1
  Abnormal
Description:  Abnormal deficits in negative geotaxis demonstrated by longer latency
Exp Paradigm:  Negative geotropism measured by hanging wire test
  Wire hang test
  P16-P18
  General locomotor activity 1
  Increased
Description:  Increased locomotor activity counts
Exp Paradigm:  Open field test
  Open field test
  3 weeks
  Size/growth 1
  Decreased
Description:  Decreased body weight
Exp Paradigm:  General observations
  General observations
  P16-P18
  Spatial reference memory 1
  Decreased
Description:  Decreased spatial reference memory indicated by longer passive avoidance latency
Exp Paradigm:  Passive Avoidance test
  Passive avoidance test
  3 weeks
  Spatial reference memory 1
  Decreased
Description:  Decreased spatial reference memory indicated by impaired water maze performance
Exp Paradigm:  Morris Water Maze Task
  Morris water maze test
  P20-P26
Grip strength1
 No change
 Wire hang test
 P13-P19
Motor coordination and balance1
 No change
 Balance beam test
 3 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_6_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Grip strength1
 No change
 Wire hang test
 3 weeks
Negative geotaxis1
 No change
 Wire hang test
 P16-P18
Righting response1
 No change
 Righting reflex test
 3 weeks
Self injurious behavior1
 No change
 General observations
 Unreported
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_7_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity 1
  Increased
Description:  Increased horizontal movements over 30 min test period in a non-social environment
Exp Paradigm:  Open field test
  Open field test
  4-6 weeks
  General locomotor activity 1
  Decreased
Description:  Decreased horizontal movements over 30 min test period in a social environment
Exp Paradigm:  Open field test
  Open field test
  4-6 weeks
  Social interaction 1
  Decreased
Description:  Decreased ano-genital sniffs indicative of social behavior deficits
Exp Paradigm:  Observation for social and play behavior in open field environment
  Open field test
  4-6 weeks
  Juvenile play 1
  Decreased
Description:  Decreased crawl-under/over playful behavior
Exp Paradigm:  Observation for social and play behavior in open field environment
  Open field test
  4-6 weeks
  Allogrooming 1
  Decreased
Description:  Decreased allogrooming behavior
Exp Paradigm:  Observation for social and play behavior in open field environment
  Open field test
  Unreported
  Apoptosis 1
  Increased
Description:  Increased levels of apoptosis detected in EGL of cerebellum and dentate gyrus of hippocampus
Exp Paradigm:  TUNEL staining of cerebellum and hippocampus
  Tunel assay
  P14
Object recognition memory1
 No change
 Open field test
 4-6 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,  

M_VPA_8_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Self grooming: perseveration 1
  Increased
Description:  Increased self grooming behavior
Exp Paradigm:  Self-Grooming Assay
  Grooming behavior assessments
  6-7 weeks
  Repetitive digging 1
  Increased
Description:  Increased stereotyped, perseverative behavior indicated by more marbles burying
Exp Paradigm:  Marble Burying Assay
  Marble-burying test
  9-10 weeks
  Anxiety 1
  Increased
Description:  Increased anxiety behavior indicated by fewer center entries
Exp Paradigm:  Open field test
  Open field test
  8-9 weeks
General locomotor activity1
 No change
 Open field test
 8-9 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_10_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Skeletal development 1
  Abnormal
Description:  Malformed pups were born at a rate of 30 to 40% which were not used for further characterization
Exp Paradigm:  General observations
  General observations
  0-3 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_11_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Skeletal development1
 No change
 General observations
 0-3 weeks
Anxiety1
 No change
 Open field test
 8 weeks
Anxiety1
 No change
 Elevated plus maze test
 8 weeks
General locomotor activity: ambulatory activity1
 No change
 Open field test
 8 weeks
Aggression1
 No change
 Resident-intruder test
 8 weeks
Rearing behavior1
 No change
 Open field test
 8 weeks
Social interaction1
 No change
 Resident-intruder test
 8 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,  

M_VPA_9_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity: ambulatory activity 1
  Decreased
Description:  Decreased distance traveled
Exp Paradigm:  Open field test
  Open field test
  4, 8 weeks
  Neuronal number 1
  Decreased
Description:  Decreased number of Nissl-positive cells in layers II/III and V of the frontal cortex and layer IV/V of the somatosensory cortex
Exp Paradigm:  Histology:Nissl staining
  Histology
  8 weeks
  Social interaction 1
  Decreased
Description:  Reduced time sniffing conspecific, male
Exp Paradigm:  Resident-intruder test
  Resident-intruder test
  4, 8 weeks
  Social interaction 1
  Increased
Description:  Increased time sniffing conspecific, female
Exp Paradigm:  Resident-intruder test
  Resident-intruder test
  8 weeks
  Rearing behavior 1
  Decreased
Description:  Decreased number of rearings
Exp Paradigm:  Open field test
  Open field test
  4, 8 weeks
  Anxiety 1
  Increased
Description:  Reduced time spent in open arms, ratio of open arm entries, increased time in closed arms
Exp Paradigm:  Elevated plus maze test
  Elevated plus maze test
  8 weeks
  Anxiety 1
  Increased
Description:  Reduced number of entries into center of open field
Exp Paradigm:  Open field test
  Open field test
  4, 8 weeks
  Anxiety 1
  Increased
Description:  Number of open arm entries
Exp Paradigm:  Elevated plus maze test
  Elevated plus maze test
  4, 8 weeks
  Spatial reference memory 1
  Decreased
Description:  Decreased time spent in target quadrant
Exp Paradigm:  Morris water maze test
  Morris water maze test
  8 weeks
  Spatial learning 1
  Decreased
Description:  Overall effect of VPA treatment on escape latency
Exp Paradigm:  Morris water maze test
  Morris water maze test
  8 weeks
Skeletal development1
 No change
 General observations
 0-3 weeks
Cognitive flexibility1
 No change
 Morris water maze test
 8 weeks
General locomotor activity1
 No change
 Morris water maze test
 8 weeks
Cortical thickness1
 No change
 Histology
 8 weeks
Allogrooming: perseveration1
 No change
 Resident-intruder test
 4, 8 weeks
Aggression1
 No change
 Resident-intruder test
 4, 8 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Immune response ,   Maternal behavior ,   Molecular profile ,   Neurophysiology ,   Physiological parameters ,   Seizure ,   Sensory ,  

M_VPA_12_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity 1
  Increased
Description:  Increased global activity
Exp Paradigm:  Open field test
  Open field test
  8 weeks
  General locomotor activity: ambulatory activity 1
  Increased
Description:  Increased distance traveled and speed
Exp Paradigm:  Open field test
  Open field test
  8 weeks
  Pain or nociception 1
  Decreased
Description:  Increased latency to withdraw paw
Exp Paradigm:  Hot plate test
  Hot plate test
  8 weeks
  Social memory 1
  Decreased
Description:  Decreased time spend in chamber with novel mouse, decreased time spent sniffing novel mouse
Exp Paradigm:  Three-chamber social approach test: social novelty
  Three-chamber social approach test
  8 weeks
  Social approach 1
  Decreased
Description:  Decreased time spent in social chamber, increased time spent in empty chamber, decreased time spent sniffing stimulus mouse
Exp Paradigm:  Three-chamber social approach test: sociability
  Three-chamber social approach test
  8 weeks
  Anxiety 1
  Decreased
Description:  Increased time spent in center of open field
Exp Paradigm:  Open field test
  Open field test
  8 weeks
  Anxiety 1
  Increased
Description:  Increased immobility in center of open field
Exp Paradigm:  Open field test
  Open field test
  8 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,  

M_VPA_19_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Dendritic architecture: spine density 1
  Decreased
Description:  VPA treated mice show a reduction in the number of dendritic spines in the dentate gyrus of the hippocampus compared to controls.
  Golgi-cox staining
  4.5 months
  Cell proliferation: neural precursors 1
  Decreased
Description:  VPA treated mice show decrease in the number of BrdU positive cells in the dentate gyrus of the hippocampus compared to controls. VPA exposure reduced DCX-positive cells in the dentate gyrus of the mouse hippocampus compared to controls.
  Immunohistochemistry
  4.5 months
  Apoptosis: brain cells 1
  Increased
Description:  VPA treated mice show an increased in the pro-apoptotic marker Bax and a reduction in the anti-apoptotic marker Bcl2 compared to controls, in the hippocampus and cerebellum.
  Immunohistochemistry
  1 month
  Social approach 1
  Decreased
Description:  VPA treated mice show decreased presence in the chamber an unfamiliar mouse, compared to controls. VPA treated mice spend more time in the central chamber compared to vehicle treated controls.
  Three-chamber social approach test
  2 weeks, 3 months
  Anxiety 1
  Decreased
Description:  VPA treated mice spent less time in the open arms of the elevated plus maze compared to controls.
  Elevated plus maze test
  2 weeks, 3 months
  Cns inflammation 1
  Increased
Description:  VPA treated mice show increase in inflammation markers iNOS and GFAP in the hippocampus and cerebellum compared to controls. VPA treated mice show increase in the inflammation marker NFkb p65 in cerebral tissue compared to controls.
Exp Paradigm:  Western Blot for Bax, Bcl-2, Inducible Nitric Oxide Synthase (iNOS), IkappaBa, Nuclear Factor-jB (NF-kB), and Glial Fibrillary Acidic Protein (GFAP) was performed.
  Western blot
  1 month
  Cns inflammation 1
  Decreased
Description:  VPA treated mice show decreased levels of IkappaB-a levels in brain tissue compared to controls.
  Western blot
  1 month
  Inflammatory response 1
  Increased
Description:  VPA treated mice show increase in chymase and tryptase in hippocampal and cerebellar tissue compared to controls indicating VPA induced inflammatory response is generated via the regulation of mast cell-derived serine peptidases,
Exp Paradigm:  Immunohistochemical Localization of Chymase, Tryptase, Tumor Necrosis Factor Alpha (TNF-a), and Interleukin-1beta (IL-1b) was perfomed.
  Immunohistochemistry
  1 month
  Cytokine levels: pro-inflammatory 1
  Increased
Description:  VPA treated mice show increase in proinflammatory cytokines TNFa and IL1beta in the brain, compared to controls.
  Western blot
  1 month
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,  

M_VPA_13_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Hyperactivity 1
  Increased
Description:  VPA exposed G1 (F1) offspring have increased hyperactivity displayed by total distance traveled in the open field
Exp Paradigm:  Males only
  Open field test
  4 weeks
  Neuroreceptor levels: glutamate receptors: ampa receptors 1
  Increased
Description:  VPA exposed G1 (F1) offspring show increased expression of the AMPA receptors GluR1 and GluR2 in the cortex
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Neuronal differentiation and specification in the brain 1
  Decreased
Description:  VPA exposed G1 (F1) offspring show reduced expression of GAD65/67 (inhibitory neuronal marker) and increased expression of PSD-95 (a post-synaptic density marker), whereas Pax6 expression was significantly decreased in the cortex, indicating impaired neuronal differentiation induced by VPA
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Neuroreceptor levels: glutamate receptors: nmda receptors 1
  Increased
Description:  VPA exposed G1 (F1) offspring show increased expression of the NMDA receptors GluN1 and GluN2B in the cortex
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Repetitive digging 1
  Increased
Description:  VPA exposure in utero causes G1 (F1) offspring show increased repetitive behavior and buried more marbles compared to controls
Exp Paradigm:  Males only
  Marble-burying test
  4 weeks
  Seizure threshold 1
  Decreased
Description:  VPA exposed G1 (F1) offspring have lower seizure threshold compared to controls
Exp Paradigm:  Males only
  Observation of electrically induced seizures
  5 weeks
  Social memory 1
  Decreased
Description:  VPA exposure in utero causes G1 (F1) offspring to manifest decreased social memory or social novelty as G1 mice do not show preference to a cage containing a stranger mouse over a familiar mouse, unlike controls
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Social approach 1
  Decreased
Description:  VPA exposure in utero causes G1 (F1) offspring to manifest impaired sociability or social approach as G1 mice do not show preference to a cage containing a stranger mouse over an empty cage, unlike controls
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Skeletal development: appendages (limbs, digits, tail) 1
  Decreased
Description:  VPA exposure in utero causes G1 (F1) offspring to develop skeletal abnormalities in the tail: crooked tail that is caused by neural tube defects
Exp Paradigm:  Males only
  General observations
  P7-4 weeks
  Anxiety 1
  Decreased
Description:  VPA exposed G1 (F1) offspring show reduced anxiety as they spend more time in the center of the open field and in the open arms of the elevated plus maze compared to controls
Exp Paradigm:  Males only-Open field test
  Open field test
  4 weeks
  Anxiety 1
  Decreased
Description:  VPA exposed G1 (F1) offspring show reduced anxiety as they spend more time in the center of the open field and in the open arms of the elevated plus maze compared to controls
Exp Paradigm:  Males only- Elevated plus maze test
  Elevated plus maze test
  4 weeks
  Protein phosphorylation 1
  Increased
Description:  VPA exposure increased phosphorylated forms of GSK3 beta, a regulator of the Wnt signaling pathway, which has been previously related to the manifestation of VPA-induced ASD phenotypes like the tail malformations
Exp Paradigm:  Males only
  Western blot
  E14
Size/growth1
 No change
 Body weight measurement
 P7-4 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Neurophysiology ,   Physiological parameters ,   Sensory ,  

M_VPA_14_IN_C_G2

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Hyperactivity 1
  Increased
Description:  Second generation (G2) mice also display increased hyperactivity in the open field test
Exp Paradigm:  Males only
  Open field test
  4 weeks
  Neuronal differentiation and specification in the brain 1
  Decreased
Description:  Second generation (G2) mice also show reduced expression of GAD65/67 (inhibitory neuronal marker), increased expression of PSD-95 (a post-synaptic density marker) and increased Pax6 expression in the cortex, compared to controls indicating persistent impaired neuronal differentiation
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Seizure threshold 1
  Decreased
Description:  Second generation (G2) mice also have lower seizure threshold compared to controls, making it a transgenerational phenotype
Exp Paradigm:  Males only
  Observation of electrically induced seizures
  5 weeks
  Social memory 1
  Decreased
Description:  Second generation (G2) mice manifest decreased social memory or social novelty and do not show preference to a cage containing a stranger mouse over a familiar mouse, unlike controls, making this a transgenerational phenotype
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Social approach 1
  Decreased
Description:  Second generation (G2) mice have imparied sociability and show reduced preference to a stranger mouse over an empty cage, compared to controls, making this a transgenerational phenotype
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Anxiety 1
  Decreased
Description:  Reduced or lack anxiety persists transgenerationally in second generation (G2) mice observed in the open field test and elevated plus maze
Exp Paradigm:  Males only-Open field test
  Open field test
  4 weeks
  Anxiety 1
  Decreased
Description:  Reduced or lack anxiety persists transgenerationally in second generation (G2) mice observed in the open field test and elevated plus maze
Exp Paradigm:  Males only- Elevated plus maze test
  Elevated plus maze test
  4 weeks
Size/growth1
 No change
 Body weight measurement
 P7-4 weeks
Skeletal development: appendages (limbs, digits, tail)1
 No change
 General observations
 
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Sensory ,  

M_VPA_15_IN_C_G3

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Hyperactivity 1
  Increased
Description:  Third generation (G3) mice also display increased hyperactivity in the open field test
Exp Paradigm:  Males only
  Open field test
  4 weeks
  Neuroreceptor levels: glutamate receptors: nmda receptors 1
  Increased
Description:  Third generation (G3) mice show increased expression of the NMDA receptors GluN1 and GluN2B in the cortex
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Neuroreceptor levels: glutamate receptors: ampa receptors 1
  Increased
Description:  Third generation (G3) mice also show persistent increased expression of the AMPA receptors GluR1 and GluR2 in the cortex
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Neuronal differentiation and specification in the brain 1
  Decreased
Description:  Third generation (G3) mice also show reduced expression of GAD65/67 (inhibitory neuronal marker), increased expression of PSD-95 (a post-synaptic density marker) and increased Pax6 expression in the cortex, compared to controls indicating persistent impaired neuronal differentiation
Exp Paradigm:  Males only
  Western blot
  4 weeks
  Repetitive digging 1
  Increased
Description:  Third generation (G3) mice also bury more marbles compared controls showing increased repetitive behavior
Exp Paradigm:  Males only
  Marble-burying test
  4 weeks
  Seizure threshold 1
  Decreased
Description:  Third generation (G3) mice also have lower seizure threshold compared to controls, making it a transgenerational phenotype over two generations
Exp Paradigm:  Males only
  Observation of electrically induced seizures
  5 weeks
  Social approach 1
  Decreased
Description:  Third generation (G3) mice have impaired sociability and show reduced preference to a stranger mouse over an empty cage, compared to controls, making this a transgenerational phenotype
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Social memory 1
  Decreased
Description:  Third generation (G3) mice manifest decreased social memory or social novelty and do not show preference to a cage containing a stranger mouse over a familiar mouse, unlike controls, making this a transgenerational phenotype
Exp Paradigm:  Males only
  Three-chamber social approach test
  4 weeks
  Anxiety 1
  Decreased
Description:  Reduced or lack anxiety persists transgenerationally in third generation (G3) mice observed in the open field test and elevated plus maze
Exp Paradigm:  Males only-Open field test
  Open field test
  4 weeks
  Anxiety 1
  Decreased
Description:  Reduced or lack anxiety persists transgenerationally in third generation (G3) mice observed in the open field test and elevated plus maze
Exp Paradigm:  Males only- Elevated plus maze test
  Elevated plus maze test
  4 weeks
  Protein phosphorylation 1
  Increased
Description:  Third generation (G3) mice have elevated levels of phosphorylated GSK3beta compared to controls making this a transgenerational phenotype
Exp Paradigm:  Males only
  Western blot
  E14
Size/growth1
 No change
 Body weight measurement
 P7-4 weeks
Skeletal development: appendages (limbs, digits, tail)1
 No change
 General observations
 
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Neurophysiology ,   Physiological parameters ,   Sensory ,  

M_VPA_16_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Neuronal number: interneurons 1
  Increased
Description:  Increased interneuron density in L4 in VPA-treated mice, but not in any other layer
Exp Paradigm:  Immunohistochemistry: Gad67
  Immunohistochemistry
  P1014
  Synaptic transmission 1
  Decreased
Description:  A shift toward greater relative inhibition at positions near, or slightly caudal to the soma of subplate neurons of VPA-treated mice when comparing to PBS controls
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Synaptic transmission: inhibitory 1
  Increased
Description:  Increased inhibitory connectivity from L5/6, L4, L2/3, and SP neurons to subplate (SP) neurons in VPA-treated mice
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Miniature post synaptic current amplitude: excitatory 1
  Increased
Description:  Increased mEPSC amplitude in VPA-treated subplate neurons relative to untreated controls
Exp Paradigm:  Whole-cell patch clamp: A1 subplate neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Synaptic transmission: excitatory 1
  Increased
Description:  Increased excitatory connectivity from L5/6 and L4 neurons to subplate (SP) neurons in VPA-treated mice
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Action potential properties: amplitude, rate of depolarization and repolarization 1
  Increased
Description:  Increased amplitude of subplate neuron IPSCs induced by activating L5/6 neurons in VPA-treated mice
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Synaptic transmission 1
  Decreased
Description:  A shift toward greater relative inhibition at the positions near the soma of the subplate neurons of VPA-treated mice when comparing to PBS controls
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P03
  Action potential properties: amplitude, rate of depolarization and repolarization 1
  Decreased
Description:  Decreased amplitude of subplate neuron EPSCs induced by activating L2/3 neurons in VPA-treated mice
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
  Sensorimotor gating 1
  Decreased
Description:  Decreaed sensorimotor gating in VPA-treated mice relative to controls
Exp Paradigm:  Acoustic startle reflex test
  Acoustic startle reflex test
  Adult
  Ultrasonic vocalization: isolation induced 1
  Decreased
Description:  Decreased number of calls of the isolation-induced ultrasonic vocalization per 5 minutes in VPA-treated mice relative to controls
Exp Paradigm:  Spectographic analysis of vocalization recordings: numbers of ultrasonic vocalization per 5 minutes
  Spectographic analysis of vocalization recordings
  P8-14
  Ultrasonic vocalization: isolation induced 1
  Decreased
Description:  Abnormal frequency histogram of the isolation-induced ultrasonic vocalization in VPA-treated mice relative to controls
Exp Paradigm:  Spectographic analysis of vocalization recordings: frequency histograms of ultrasonic vocalization
  Spectographic analysis of vocalization recordings
  P2
Ultrasonic vocalization: isolation induced1
 No change
 Spectographic analysis of vocalization recordings
 P2
Neuronal number1
 No change
 Immunohistochemistry
 P13
Miniature post synaptic current amplitude: inhibitory1
 No change
 Whole-cell patch clamp
 P1014
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp
 P1014
Miniature post synaptic current frequency: inhibitory1
 No change
 Whole-cell patch clamp
 P1014
Neuroreceptor activity1
 No change
 Whole-cell patch clamp
 P0-14
Synaptic transmission1
 No change
 Whole-cell patch clamp
 P47
 Not Reported: Circadian sleep/wake cycle ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Social behavior ,  

M_VPA_17_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Action potential properties: amplitude, rate of depolarization and repolarization 1
  Decreased
Description:  No change in the amplitude of subplate (SP) neuron EPSCs induced by activating L2/3, L4, L5/6, or SP neurons in VPA-treated mice
Exp Paradigm:  Laser scanning photostimulation; Whole-cell patch clamp: primary auditory cortex A1 neurons in acute thalamocortical slices
  Whole-cell patch clamp
  P1014
Action potential properties: amplitude, rate of depolarization and repolarization1
 No change
 Whole-cell patch clamp
 P1014
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp
 P1014
Synaptic transmission: inhibitory1
 No change
 Whole-cell patch clamp
 P1014
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,   Social behavior ,  

M_VPA_18_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Social approach 1
  Decreased
Description:  VPA treated mice showed less preference for a mouse than an inanimate object compared to controls.
  Three-chamber social approach test
  6 weeks
  Social approach 2
  Decreased
Description:  VPA exposed mice show decrease in time spent interacting with a conspecific over an empty cup compared with controls.
  Three-chamber social approach test
  7-10 weeks
  Social memory 1
  Decreased
Description:  VPA treated mice showed less preference for an unfamiliar mouse than a familiar mouse compared to controls.
  Three-chamber social approach test
  6 weeks
  Intestinal microbiota composition: overall microbiota composition 2
  Abnormal
Description:  VPA exposed mice show alterations in gut bacterial composition compared with controls.
  16s rrna gene sequence analysis for identification of bacteria
  7-10 weeks
  Bioactive compound levels: serotonin 1
  Increased
Description:  VPA treated mice show increased levels of serotonin in the serum compared to controls.
Exp Paradigm:  Serum levels of serotonin were measured in blood drawn from the mandibular vein.
  Elisa
  6 weeks
  Intestinal microbiota composition: species diversity 1
  Abnormal
Description:  VPA treated mice showed an overall composition of gut microbes of ASD mice comaparable to that in control mice at the phylum level. VPA treated mice show a slight increase in Firmicutes and a slight decrease in Bacteroidetes compared to controls. VPA treated mice show decreased diversity of microbial species (alpha diversity) in the feces compared to controls. VPA treated mice show changes in specific microbial taxa compared to control mice, that recapitualte change in ASD patients (Increased: Lachnospiraceae, Parabateroides, Rikenellaceae, Dorea, Bilophila, Enterococcus, Megasphaera, Peptostreptococcacea, Desulfovibrio, Sporanaerobacter; Decreased: Coriobactericaceae, Distasonis, Erysipelotrichaceae, Oscillospira, Prevotella).
Exp Paradigm:  Maternal and offspring feces were used for DNA extraction. Two alpha-diversity indexes (PD index and Shannon index) were computed. Relative abundance analysis of gut microbiota of mice at various taxonomic levels ranging from phylum to species was performed.
  16s rrna gene sequence analysis for identification of bacteria
  3 weeks
  Intestinal microbiota composition: species diversity 2
  Abnormal
Description:  VPA exposed mice show alterations in gut microbiota species diversity compared with controls.
  16s rrna gene sequence analysis for identification of bacteria
  7-10 weeks
  Anxiety 1
  Increased
Description:  VPA treated mice spent less time in the center of the open field.
Exp Paradigm:  Time spent in the center of the open field was measured.
  Open field test
  6 weeks
General locomotor activity: ambulatory activity1
 No change
 Open field test
 6 weeks
Intestinal microbiota composition: overall microbiota composition1
 No change
 16s rrna gene sequence analysis for identification of bacteria
 3, 4, 5 weeks
Intestinal microbiota composition: species diversity2
 No change
 Quantitative pcr (qrt-pcr)
 7-10 weeks
Social memory2
 No change
 Three-chamber social approach test
 7-10 weeks
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Motor phenotype ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,  

M_VPA_20_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  General locomotor activity: ambulatory activity 1
  Increased
Description:  VPA exposed male mice travelled longer distances compared with controls.
  Open field test
 
  Oxidative stress in neurons 1
  Increased
Description:  VPA exposed mice show increased levels of MDA and ROS, decreased activity of SOD and GSH-Px, and decreased content of GSH, compared with controls, in the hippocampus and amygdala.
  Enzyme assay
 
  Repetitive digging 1
  Increased
Description:  VPA exposed male mice buried more marbles compared with controls.
  Marble-burying test
 
  Social approach 1
  Decreased
Description:  VPA exposed male mice exhibit lower social index compared with controls.
  Three-chamber social approach test
 
  Social memory 1
  Decreased
Description:  VPA exposed mice showed decrease in social preference of a novel mouse over a familiar mouse compared with controls.
  Three-chamber social approach test
 
  Depression 1
  Increased
Description:  VPA exposed male mice remained immobile for longer times compared with controls.
  Tail suspension test
 
  Microgliosis 1
  Increased
Description:  VPA exposed male mice show increase in levels of activated microglia compared with controls, in the hippocampus and amygdala.
  Immunofluorescence staining
 
  Cns inflammation 1
  Increased
Description:  VPA exposed male mice show increased levels of IL-1beta, IL-6 and TNFalpha compared with controls.
  Cytokine level detection
 
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Learning & memory ,   Maternal behavior ,   Molecular profile ,   Neuroanatomy / ultrastructure / cytoarchitecture ,   Physiological parameters ,   Seizure ,   Sensory ,  

M_VPA_21_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Dendritic architecture: spine density 1
  Decreased
Description:  Prenatal exposure to VPA shows decreased spine density in the somatosensory cortex compared with controls.
  Golgi-cox staining
  Adult
  Social interaction 1
  Decreased
Description:  Prenatal exposure to VPA shows decreased sniffing and allogrooming of the intruder compared to controls.
  Resident-intruder test
  10 weeks
  Gene expression 1
  Increased
Description:  Prenatal exposure to VPA shows increased transcript levels of Rest compared with controls in the somatosensory cortex.
  Quantitative pcr (qrt-pcr)
  Adult
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 Adult
 Not Reported: Circadian sleep/wake cycle ,   Communications ,   Developmental profile ,   Emotion ,   Immune response ,   Learning & memory ,   Maternal behavior ,   Motor phenotype ,   Neurophysiology ,   Physiological parameters ,   Repetitive behavior ,   Seizure ,   Sensory ,  

M_VPA_22_IN_C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
  Cell proliferation: neural precursors 1
  Decreased
Description:  VPA exposed mice show decrease in BrdU incorporated cells in the hippocampus compared with controls, particularly in the subgranular zone. VPA exposed mice show decrease in DCX positive immature neurons in the hippocampus compared with controls, particularly in the subgranular zone.
Exp Paradigm:  hippocampus; dentate gyrus; adult male mice were injected BrdU intraperitoneally every 12 hours for 3 times
  Immunohistochemistry
  Adult
  Self grooming: perseveration 1
  Increased
Description:  VPA exposed mice show increased self-grooming compared with controls.
  Grooming behavior assessments
  8 weeks
  Social approach 1
  Decreased
Description:  VPA exposed mice show greater preference for the novel object than for the novel mouse compared with controls.
  Three-chamber social approach test
  8 weeks
  Social memory 1
  Decreased
Description:  VPA exposed mice show greater preference for the familiar mouse than for the novel mouse compared with controls.
  Three-chamber social approach test
  8 weeks
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 P15
Rearing behavior1
 No change
 Novel cage test
 8 weeks
 Not Reported:
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