Role of GABAA receptors and chloride transporters in autism - An explorative analysis using peripheral blood as a model.

BACKGROUND: Gamma-aminobutyric acid (GABA), acting through its receptors, is the principal inhibitory neurotransmitter in the brain. It plays a vital role in maintaining neuronal chloride balance by interacting with chloride co-transporters, mainly NKCC1 and KCC2. In addition to the neurons, GABA receptors and chloride co-transporters are found to be expressed by the immune cells also. This present work aimed to study the gene expression patterns of GABAA receptors and chloride co-transporters (NKCC1 and KCC2) in the autism-affected children of West Bengal using peripheral blood as model.

METHODS AND RESULTS: 95 ASD-affected (case) and 82 neurotypical (control) children were recruited for this study. Gene expression patterns were measured by qRT-PCR method. Plasma chloride and GABA levels were estimated by the biochemical method and ELISA respectively. PBMC was cultured in vitro for 72 h with and without Resveratrol and Bumetanide treatment following standard protocols to explore potential change of gene expression. Significant lower expression levels of GABAA type receptor subunits and KCC2 were observed in PBMC of ASD cases compared to controls. These alterations were associated with higher plasma GABA levels and lower plasma chloride concentrations in the ASD group. Preliminary data showed that in vitro treatment with Resveratrol and Bumetanide partially affected the expression level of KCC2 and GABAA receptor subunits in PBMCs of the ASD group.

CONCLUSION: Overall, the findings demonstrated an association between altered peripheral GABA-related gene expression, disrupted chloride homeostasis and autism pathology for the first time in an affected Indo-Caucasoid population from West Bengal, India.