Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

Abstract

An intriguing novel pathophysiological insight into mood disorders is the notion that one's metabolic status influences mood. In rodents, cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1/NUCB2 have not only been implicated in metabolism, but in the pathobiology of anxiety and depressive- like behaviour, however they have not previously been investigated in depressed subjects. Both peptides are highly expressed in centrally projecting neurons in the Edinger- Westphal nucleus (EWcp) in the midbrain. The EWcp has been implicated in stress adaptation and stress-related mood disorders like major depressive disorder in a sex-specific manner. This is intriguing, given the fact that females have higher prevalence of mood disorders. Here, we hypothesized that the expression of CART and nesfatin-1 in EWcp would exhibit a sex-specific difference between depressed suicide victims vs. controls. We found that CART and nesfatin/NUCB2 colocalized in the human EWcp, and that CART mRNA content was much higher in both male (x3.8) and female (x5.9) drug-free suicide victims than in controls (persons who died without any diagnosed neurodegenerative or psychiatric disorder). Similarly, NUCB2 mRNA content was also higher (x1.8) in male suicides, whereas in female suicide victims, these contents were x2.7 lower compared to controls. These observations are the first to show changes in the dynamics of CART and nesfatin/NUCB2 expressions in the midbrain of drug-free depressed suicide victims vs. controls. This article is part of a Special Issue entitled 'Anxiety and Depression'.