Lept Go! GABA switches action during brain development, neuronal excitation first and later on, around birth, inhibition. Alteration in this timing sets up conditions for future neurological disorders and cognitive deficits. Here, the authors uncover a new role for leptin in this process, an hormone regulating weight and whose elevation during pregnancy heightens the risk of autistic syndromes for incoming kids. Authors fill the gaps showing that maternal obesity in rodents delays the GABA switch in neurons. (by Ingrid Bureau)
Scientific abstract: Brain computations rely on a proper balance between excitation and inhibition which progressively emerges during postnatal development in rodent. γ-Aminobutyric acid (GABA) neurotransmission supports inhibition in the adult brain but excites immature rodent neurons. Alterations in the timing of the GABA switch contribute to neurological disorders, so unveiling the involved regulators may be a promising strategy for treatment. Here we show that the adipocyte hormone leptin sets the tempo for the emergence of GABAergic inhibition in the newborn rodent hippocampus. In the absence of leptin signaling, 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.
Published in eLIFE, August 2018
More work from the group here