Changes in the Expression of SNAP-25 Protein in the Brain of Juvenile Rats in Two Models of Autism

Abstract

The results of genetic studies suggest a possible role for SNAP-25 polymorphism in the development of autism spectrum disorders (ASDs); however, there are no data available on whether changes in SNAP-25 expression also affect animals in rodent models of ASD. The aim of the present study was to explore this issue. The studies included 1-month-old rats representing valproic acid (VPA)-and thalidomide (THAL)-induced models of autism. Their mothers received single doses of VPA (800 mg/kg) or THAL (500 mg/kg) per os on the 11th day of gestation. SNAP-25 protein content in the cerebellum, hippocampus, and frontal lobe was determined using Western blotting, while changes of mRNA levels of Snap25 gene were determined using real-time polymerase chain reaction. Compared to controls, SNAP-25 content was decreased by approximately 35% in all brain structures tested, in both males and females, exclusively in the VPA group. In contrast to this, Snap25 expression, studied in males, was increased in the hippocampus and cerebellum in both, VPA-and THAL-treated rats. We discuss the compliance of these results with the hypothesized role of SNAP-25 in the pathophysiology of ASD and the adequacy of the experimental models used.

Head-to-Head Study of Developmental Neurotoxicity and Resultant Phenotype in Rats: α-Hexabromocyclododecane versus Valproic Acid, a Recognized Model of Reference for Autism Spectrum Disorders

“…Opposite results were obtained according to the exposure to VPA (16% decrease) or to α-HBCDD (19% increase, p = 0.082) compared to controls, thus inducing a 30% difference between these two groups (p = 0.082). A decrease in SNAP25 in the frontal lobe of the animals in the VPA model has already been reported [48]. In parallel, the results obtained for α-HBCDD are consistent with those observed for tetrabromobisphenol-A (TBBPA; another flame retardant), for which an increase in SNAP25 was observed after in-vitro exposure of primary rat cerebellar granule cell cultures [49].…”

Zinc and Copper Brain Levels and Expression of Neurotransmitter Receptors in Two Rat ASD Models

“…In our previous works (Lenart et al, 2020b;Toczylowska et al, 2020), we did not find significant statistical differences between males and females within the study group. Therefore, we decided to perform our first screening test of genes encoding proteins of selected receptors, involved in the pathogenesis of ASD, on males, in which we observed slightly greater changes than in females.…”

SCGN deficiency is a risk factor for autism spectrum disorder

“…The resulting network suggested that SCGN regulated the oxytocin and the immune response pathways via SNAP-25, whose abnormal expressions and/or mutations have been associated with ASD and other neurological disorders. 16 We found that 24 genes, including Camk2b, Adcy5, Cacna2d3, Camk2a, Itpr1, Plcb1, Prkcb, Mef2c , and Ptgs2 , were ASD-risk genes that were involved in the oxytocin pathway. Among them, CAMK2A and CAMK2B are Calcium/calmodulin-dependent protein kinase II (CaMKII) isoforms with pivotal roles in neuronal development.…”

“…In recent years, studies including genome-wide sequencing technologies have revealed a large set of ASD-risk genes, [11][12][13][14] which are often associated with a number of biological functions/pathways, including synaptic structure and functions (e.g., SNAP-25, STXBP2, SHANK3, and NLGN3), chromatin modification (e.g., CHD7 and MECP2), Wnt signaling (e.g., CHD8, PAX5, and ATRX), oxytocinergic signaling, immune function, and mitochondrial function, among other processes. 2,[15][16][17] One emerging concept in the field is that these pathways could converge on the regulation of a few key functional activities. For instance, the loss of synaptic adhesion molecule Nlgn3 impairs oxytocin signaling and disrupts normal translation.…”