Neuroprotective effects of overexpression of the inhibitor of apoptosis proteins in the quinolinic acid model of excitotoxic injury.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder which results in the selective loss of the medium spiny neurons in the striatum. The neuropathological and behavioural deficits of HD can be modeled in rats by injection of the NMDA receptor agonist quinolinic acid (2,3 pyridine decarboxylate; QA) directly into the striatum. The first aim of this study was to examine whether intrastriatal QA injections result in neurons dying by apoptosis as assessed by caspase activation. Animals were intrastriatally injected with QA and striatal brain sections processed for several apoptotic markers. Recently, a novel family of inhibitor of apoptosis (IAP) proteins have been identified and subsequently shown to attenuate cell death induced by a variety of apoptotic triggers in vitro. The goal of the second study was to determine whether adenovirally-mediated overexpression of the IAPs resulted in protection against QA-induced degeneration. The goal of the third study was to determine whether neurons saved by overexpression of the IAPs were still functional. In a third study, animals were intrastriatally injected with recombinant adenoviral constructs containing either xiap, naip, or lacZ one week prior to QA injections (120 nmol). (Abstract shortened by UMI.