N-acetylcysteine (nac) in huntington’s disease (hd) and affective-like disorders

Huntington’s disease (HD) is a devastating autosomal dominant disease which is usually diagnosed when locomotor symptoms start to be noticeable (e.g. abnormal involuntary writhing movements called chorea). While there is currently no cure for HD, we recently published beneficial effects of chronic treatment with the antioxidant drug, N-Acetylcysteine (NAC) on locomotor deficits in HD mice [1] Psychiatric disorders often precede the locomotor symptoms in HD patients. Our group was the first to discover a depressive endophenotype in a mouse model of HD [2]. Our new pilot data suggest that NAC treatment is also able to correct the depression-like behaviour displayed by HD mice. Alongside the ‘neurotransmitter hypothesis’ of depression (e.g. serotonin and glutamate signalling), new evidence suggests that chronic inflammation and oxidative stress are implicated in the pathophysiology of depression. Dysregulation in those pathways (which are all linked altogether) would ultimately affect the hypothalamic–pituitary–adrenal (HPA) axis function as well as neurogenic processes known to be involved in affective function. Our molecular pilot data suggest that chronic NAC is able to correct glutamatergic receptor dysfunction in HD mice. We also propose to study potential antidepressant-like effect of NAC in other mouse models of affective-like disorders.