In utero exposure to valproic acid and autism — A current review of clinical and animal studies
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...In addition, high doses of the monocarboxylic HDAC inhibitors propionate or valproate, administered either systemically to the mother during pregnancy or intraventricular in adulthood were repeatedly shown to induce autistic-like symptoms in animal models (Chomiak et al., 2013; Macfabe, 2012; MacFabe et al., 2011, 2007; Roullet et al., 2013; Thomas et al., 2012), suggesting extreme care has to be given to evaluation of the potential use of SCFAs in treatment of ASDs....
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Cites background from "In utero exposure to valproic acid ..."
...The case for in utero valproate as a causal risk factor for ASC has been strengthened by its use to create one of the most influential animal models of the condition: rats and mice exposed to it in utero show a profile of behavioural features that may correspond to the social, communication and flexibility difficulties seen in humans with ASC (Roullet et al., 2013)....
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...In utero valproate exposure in humans is associated with an array of neurodevelopmental atypicalities beyond ASC, including attention-deficit/hyperactivity disorder (ADHD), dyspraxia and low IQ (Roullet et al., 2013)....
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...…strengthened by its use to create one of the most influential animal models of the condition: rats and mice exposed to it in utero show a profile of behavioural features that may correspond to the social, communication and flexibility difficulties seen in humans with ASC (Roullet et al., 2013)....
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References
1,785 citations
"In utero exposure to valproic acid ..." refers background in this paper
...In vitro, VPA increased histone H4 acetylation (AcH4) in a dose-dependent manner in several types of transformed cells (Gottlicher et al., 2001)....
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1,607 citations
"In utero exposure to valproic acid ..." refers background in this paper
...This finding has clinical relevance as it aimed to better understand the basis for the male:female imbalanced ratio in autism (Fombonne, 2003)....
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1,564 citations
1,232 citations
"In utero exposure to valproic acid ..." refers methods in this paper
...a Three chamber social behavior apparatus is an established tool for testing sociability and social novelty (Moy et al., 2004); for sociability test, chamber 1 contains a stranger mouse or rat in an inverted cup, the center chamber is empty, and chamber 2 contains an empty inverted cup; for social novelty, chamber 1 contains a familiar mouse or rat in an inverted cup, the center chamber is empty, and chamber 2 contains a stranger mouse or rat in an inverted cup....
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...− Gandal et al. (2010) a Three chamber social behavior apparatus is an established tool for testing sociability and social novelty (Moy et al., 2004); for sociability test, chamber 1 contains a stranger mouse or rat in an inverted cup, the center chamber is empty, and chamber 2 contains an empty…...
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743 citations
"In utero exposure to valproic acid ..." refers background in this paper
...+ Schneider and Przewlocki (2005) and Schneider et al. (2008) t2:6 Adult rats placed in a three-chamber apparatusa VPA rats spent more time in the empty chamber, but did not otherwise show any signs of social behavior deficits....
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...5–12.5 P11 Reduced number of cranial motor neurons in VPA-treated Rodier et al. (1996) t3:9 400 mg/kg t3:10 Sprague Dawley rat E7, E9....
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...Several publications have examined the impact of in utero exposure to VPA on social behavior and stereotypic behaviors (Kataoka et al., 2011; Markram et al., 2008; Roullet et al., 2010; Schneider and Przewlocki, 2005)....
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...Another study (Markram et al., 2008) has reported deficits in social interactions and increased stereotypic behaviors in the Y maze in VPA-treated rats (500 mg/kg)....
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...5 Postnatal and adult time points Autistic-like behaviors in VPA-treated Enrichment reduced autistic-like behaviors in VPA-treated Schneider and Przewlocki (2005) and Schneider et al. (2006) t3:22 C57BL/6 mice E13 P0–P70 Reduced postnatal and adult USVs, reduced social preference, increased self-grooming, and deficits in pre-pulse inhibition in VPA-treated Gandal et al. (2010) t3:23 6 wk+ Increased repetitive behaviors and reduced center entries in the open field in VPA-treated mGluR5-receptor antagonist treatment reduced repetitive behaviors but did not affect open field behavior Mehta et al. (2011) t3:24 800 mg/kg t3:25 Heterogeneous Strain 1 mice E11 P9–P25 Developmental delay in eye opening and olfactory discrimination, reduced social interaction in VPA-treated Roullet et al. (2010) t3:26 P60 Reduced levels of brain derived neurotrophic factor in somatosensory cortex in VPA-treated Reduced levels of neuroligin 3 in hippocampus and somatosensory cortex in VPA-treated Kolozsi et al. (2009) and Roullet et al. (2010) t3:27 Sprague Dawley rat E9 P50 Reduced monoamine levels in brain tissue from VPA-treated Narita et al. (2002) t3:28 5–14 wk Subtle differences in radial arm maze and open field test; no difference in social behavior Narita et al. (2010) t3:29 Wistar rat E9 P7, P12 P63–80 Increased righting time P12 in VPA-treated Elevated basal dopamine levels and increase DA during swim stress in VPA-treated Nakasato et al. (2008) t3:30 P28–43 Hyperactivity in a novel environment, disruptions in circadian rhythm, and increased levels of serotonin in frontal cortex in VPA-treated Tsujino et al. (2007) t3:31 Other t3:32 Wistar rat 470 or 720 mg/kg throughout gestation P15–70 Reduced latency geotaxis, increased activity in open field at P15 in 470 mg/kg VPA-treated Reduced latency to fall from rotorod, increased time in Morris Water Maze probe trial, and reduced cortical volume in 720 mg/kg VPA-treated with correlation of probe trial and brain volume Frisch et al. (2009) t3...
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