When leptin and metabolism impact the actions of GABA on immature neurons

An interesting observation linking metabolism with the GABA developmental shift and developmental disorders. Studying the well characterized GABA developmental shift with excitatory actions of GABA on immature neurons and inhibitory ones in adults, J-L Gaiarsa, C Porcher and colleagues have tested the hypothesis that metabolism and a major hormone controlling it -leptin- impact the time course of the shift. They show indeed that the adipocyte hormone leptin sets the tempo for the emergence of GABAergic inhibition in the newborn rodent hippocampus. In the absence of leptin signalling, hippocampal neurons show an advanced emergence of GABAergic inhibition. Conversely, maternal obesity associated with hyperleptinemia delays the excitatory to inhibitory switch of GABA action in offspring. This study uncovers a developmental function of leptin that may be linked to the pathogenesis of neurological disorders and helps understanding how maternal environment can adversely impact offspring brain development.

Importantly, this study unravels the importance of biological parameters on early brain development and how this impact intracellular chloride levels and the polarity of GABA actions. Therefore, the timing of the shift exerts major effects on the pathogenesis of brain disorders in line with our studies on the links between this shift and Autism Spectrum Disorders (Tyzio et al, Science, 2014). It is conceivable therefore that different hormones impact the developmental shift with different time courses and that collectively these contribute when disturbed to many developmental disorders. The links between obesity, hypertension and other parameters during pregnancy and delivery and brain disorders are well established. Clearly determining how early networks mature and are impacted by genetic or environmental insults is instrumental to understand and treat brain disorders.

Source: https://www.ncbi.nlm.nih.gov/pubmed/30106375

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