title: 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 (×3.8) and female (×5.9) drug-free suicide victims than in controls (persons who died without any diagnosed neurodegenerative or psychiatric disorder). Similarly, NUCB2 mRNA content was also higher (×1.8) in male suicides, whereas in female suicide victims, these contents were ×2.7 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'.
authors.affiliation: Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, 6525 AJ Nijmegen, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bloem
authors.forename: Lu
authors.initials: L
authors.lastname: Xu
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
authors.forename: Gábor
authors.initials: G
authors.lastname: Faludi
authors.forename: Miklós
authors.initials: M
authors.lastname: Palkovits
authors.forename: Eric W
authors.initials: EW
authors.lastname: Roubos
authors.forename: Tamás
authors.initials: T
authors.lastname: Kozicz
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D042282:Microdissection; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics; D013405:Suicide / Q000523:psychology*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein