Activation of cyclic GMP-dependent protein kinase blocks alcohol-mediated cell death and calcium disruption in cerebellar granule neurons.

ABSTRACT: Alcohol during brain development leads to the widespread neuronal death observed in fetal alcohol spectrum disorders (FASD). In comparison, the mature brain is less vulnerable to alcohol. Studies into maturation-acquired alcohol resistance uncovered a protective mechanism that reduces alcohol-induced neuronal death through nitric oxide-cGMP-cyclic GMP-dependent protein kinase (NO-cGMP-cGK) signaling. However, the downstream processes underlying this neuroprotection remain unclear. Alcohol can disrupt levels of intracellular calcium ([Ca²⁺]_i) in vulnerable neuronal populations to trigger cell death in both in vivo and in vitro models of FASD. Since cGK has been demonstrated to regulate and inhibit intracellular Ca²⁺ release, we examined the hypothesis that c

SUBMITTER: Kouzoukas DE 

PROVIDER: S-EPMC6190832 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature