Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission
(2017)
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- The amyloid precursor protein, APP, is critically involved in the pathophysiology of Azheimer’s disease (AD). APP is known to modulate synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by changes in intracellular chloride concentration regulated by Na+-K+-2Cl- cotransporter 1 (NKCC1) and neuronal K+-Cl- cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling polarity. Here, we demonstrated that APP affected this GABA shift. Indeed, we observed that expression of APP decreased KCC2 expression both in vitro and in vivo and that this decrease was associated with a less inhibitory and less hyperpolarizing GABAergic signaling. In addition, KCC2 expression was also shown to be decreased in the cortex of sporadic AD patients. These results argue for a key role of APP in the regulation of GABAergic neurotransmission and shed light on new mechanisms that could contribute to AD pathophysiology.
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Doshina, A. (2017). Cortical cells reveal APP as a new player in the regulation of GABAergic neurotransmission. https://hdl.handle.net/2078.5/178035