Plasmin-mediated degradation of laminin gamma-1 is critical for ethanol-induced neurodegeneration.

ABSTRACT:

Background

Alcoholism may result in severe neurological deficits and cognitive impairments. Many of the central effects of ethanol (EtOH) can be explained by upregulation of N-methyl-D-aspartate (NMDA) and downregulation of gamma-aminobutyric acid (GABA) A receptors (GABAA) in response to long-term EtOH consumption. Abrupt ethanol withdrawal (EW) may result in neuronal hyperexcitability leading to hallucinations, seizures, neurodegeneration, and sometimes death.

Methods

Using a multidisciplinary approach in wild-type and genetically modified mice, we examined the contribution of the tissue plasminogen activator (tPA), plasminogen, and laminin to EW-induced cell death.

Results

Here we show that EW-induced neurodegeneration is mediated by the tPA/plasmin system. During

SUBMITTER: Skrzypiec AE 

PROVIDER: S-EPMC2757483 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature