Human SLC17A7 peptide

There is a hypothesis of the involvement of the glutamatergic system in the development of autism. It has been shown that the chronic experience in daily intermale confrontations leads to disturbances in social behavior: a decrease in communicativeness, disturbances of socialization, emergence of stereotypical behaviors that can be considered as symptoms of the autistic spectrum disorders. So, the aim of this study was to investigate changes in the expression of glutamatergic (GG) and autism-related (GA) genes in the hippocampus of animals with impaired social behavior caused by repeated experience of social defeat or aggression in daily agonistic confrontations. To form groups of animals with contrasting behaviors, a model of sensory contact (chronic social stress) was used. The collected brain samples were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). Transcriptomic analysis revealed a down-regulation of autism-related (Shank3, Auts2, Ctnnd2, Nrxn2) and glutamatergic (Grm4) genes in aggressive mice. At the same time, the expression of GA-related genes (Shank2, Nlgn2, Ptcdh10, Reln, Arx) and GG genes (Grik3, Grm2, Grm4, Slc17a7, Slc1a4, Slc25a22) excluding Grin2a was increased in defeated mice. Correlative analysis revealed a statistically significant association between GG and GA expression. These results can serve as a confirmation of the participation of the glutamatergic system in the pathophysiology of the autistic spectrum disorder.

In adult neocortex, VGLUT1 (also known as SLC17A7), the main glutamate vesicular transporter, and VGAT (also known as SLC32A1), the gamma-aminobutyric acid (GABA) vesicular transporter, are co-expressed in a subset of axon terminals forming both symmetric and asymmetric synapses, where they are sorted into the same vesicles. However, the functional consequence of this colocalization in cortical neurons has not been clarified. Here, we tested the hypothesis that cortical axon terminals co-expressing VGLUT1 and VGAT can evoke simultaneously monosynaptic glutamate and GABA responses, and investigated whether the amount of terminals co-expressing VGLUT1 and VGAT is affected by perturbations of excitation-inhibition balance. In rat primary cortical neurons, we found that a proportion of synaptic and autaptic responses were indeed sensitive to consecutive application of selective glutamate and GABA(A) receptor blockers. These 'mixed' synapses exhibited paired-pulse depression. Notably, reducing the activity of the neuronal network by treatment with glutamate receptor antagonists decreased the amount of 'mixed' synapses, whereas reducing spontaneous inhibition by treatment with bicuculline increased them. These synapses might contribute to homeostatic regulation of excitation-inhibition balance.