N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease

Abstract

Glutamatergic dysfunction has been implicated in the pathogenesis of depressive disorders and Huntington's disease (HD), in which depression is the most common psychiatric symptom. Synaptic glutamate homeostasis is regulated by cystinedependent glutamate transporters, including GLT-1 and system xc -. In HD, the enzyme regulating cysteine (and subsequently cystine) production, cystathionine-γ-lygase, has recently been shown to be lowered. The aim of the present study was to establish whether cysteine supplementation, using N-acetylcysteine (NAC) could ameliorate glutamate pathology through the cystine-dependent transporters, system xc - and GLT-1. We demonstrate that the R6/1 transgenic mouse..