Long-lasting Behavioral and Neuroanatomical Effects of Postnatal Valproic Acid Treatment. (10th May 2020)

• Record Type: Journal Article
• Authors: Norton, Sara A.; Gifford, Janace J.; Pawlak, Anthony P.; Derbaly, Anna; Sherman, Sara L.; Zhang, Huaye; Wagner, George C.; Kusnecov, Alexander W.
• Is Part Of: Neuroscience. Volume 434(2020)
• Page Start: 8
• Page End: 21
• Publication Date: 2020-05-10
• Subjects: 5-HT serotonin -- ASD autism spectrum disorder -- AUDp primary auditory cortex -- EPM elevated plus maze -- HWR height:width ratio -- mPFC medial prefrontal cortex -- PC pyramidal cell -- PFC prefrontal cortex -- PPI prepulse inhibition -- VPA valrpoic acid -- yFP yellow flourescent protein; Valproic acid -- Disinhibition -- Impulsivity -- Aggression -- Autism spectrum disorder -- ADHD; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.02.029
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Male mice treated postnatally with VPA demonstrated increased aggression at P30. VPA-treated male mice had decreased avoidance of the open arms in the EPM on P91. VPA-treated male mice displayed impaired reversal learning in adulthood. Dendritic spine density was decreased in the mPFC of VPA-treated mice on P30–35. Dendritic spine morphological abnormalities were observed in both the mPFC and AUDp of VPA-treated mice. Abstract: Valproic acid (VPA) administered to mice during the early postnatal period causes social, cognitive, and motor deficits similar to those observed in humans with autism spectrum disorder (ASD). However, previous studies on the effects of early exposure to VPA have largely focused on behavioral deficits occurring before or during the juvenile period of life. Given that ASD is a life-long condition, the present study ought to extend our understanding of the behavioral profile following early postnatal VPA into adulthood. Male mice treated with VPA on postnatal day 14 (P14) displayed increased aggression, decreased avoidance of the open arms in the elevated plus maze, and impaired reversal learning in the Y maze. This may indicate a disinhibited or impulsive phenotype in male, but not female, mice treated with VPA during the second week of postnatal life. Decreased dendritic spine density and dendritic spine morphological abnormalities in the mPFC of VPA-treated mice may be indicative of PFC hypofunction, consistent with the observed behavioral differences. Since these types of long-lasting deficits are not exclusively found in ASD, early life exposure to VPA may reflect dysfunction of a neurobiological domain common to several developmental disorders, including ASD, ADHD, and conduct disorder.