Altered morphology of motor cortex neurons in the VPA rat model of autism

Abstract

Autism occurs in 1 in 1,000 children and incidence may be increasing. Investigating brain development and developmental injury in humans is difficult. As such, many studies rely on animal models of disorders. We chose to investigate the valproic acid-exposed rat, as this model shares many similarities with autism. Pregnant Long-Evans rats were administered either valproic acid (VPA) or saline during fetal neural tube development. Morphological analyses of cells in layer II of the golgi impregnated motor cortex were done to determine dendritic length, volume, and complexity in both groups. No differences were found in length or volume of cortical dendrites, but dendritic arborization was more complex in apical dendrites of pyramidal cells in VPA-exposed animals than controls. The implication of this finding is that pruning in the VPA-exposed rat is not occurring, which is consistent with theories related to abnormal human brain development in autism.

Effects of Rat Prenatal Exposure to Valproic Acid on Behaviour and Neuro-Anatomy

“…Taken in conjunction with previous work [1,4,5,7,9], the current study supports the conclusion that prenatal exposure of pregnant rats to VPA on G12 may provide a viable rodent model for the study of autism insofar as the behavioural and neuro-anatomical findings are reliable and consistent with some of the human literature. For summary of these results see table 2.…”

“…In the VPA rat model of autism, VPA is administered to pregnant dams on the 12th day of gestation. Many studies have examined individual autism-specific deficits associated with the VPA rat model, including morphology of motor cortex neurons [4], cerebellar anomalies [5], immunological alterations [6], repetitive behaviours [7], electrophysiological evoked response latency [8], and social-emotional functioning [9,10]. To our knowledge, however, there has not been a comprehensive examination of the viability of the VPA rat model of autism, at the neuro-anatomical and behavioural level.…”

Environmental Factors in the Aetiology of Autism – Lessons from Animals Prenatally Exposed to Valproic Acid

“…Thus, increased serotonin level in VPA rats may be one of the factors triggering altered developmental patterns observed in this model. Indeed, a more complex dendritic arborization in apical dendrites of pyramidal cells in motor cortex had been shown in VPA-exposed animals (Snow et al, 2008), suggesting disturbed pruning process, which is consistent with theories related to abnormal human brain development in autism. VPA rats also express altered functioning of opioidergic and glutamatergic systems.…”

Increased sociability and gene expression of oxytocin and its receptor in the brains of rats affected prenatally by valproic acid

“…impairment related to autism have used similar number of litters as we used in our study (Bambini-Junior et al, 2014;Martin and Manzoni, 2014;Miyazaki et al, 2005;Oyabu et al, 2013;Walcott et al, 2011;Tashiro et al, 2011;Snow et al, 2008;Tsujino et al, 2007). The elevated level of behaviour reflecting fear of the adult male used as the stranger rat was not observed.…”