Abstract
Changes in sphingolipid metabolism have been suggested to contribute to the pathophysiology of major depression. In this study, we investigated the activity of acid and neutral sphingomyelinases (ASM, NSM) and ceramidases (AC, NC), respectively, in twelve brain regions of female rats selectively bred for high (HAB) versus low (LAB) anxiety-like behavior. Concomitant with their highly anxious and depressive-like phenotype, HAB rats showed increased activity of ASM and NSM as well as of AC and NC in multiple brain regions associated with anxiety- and depressive-like behavior, including the lateral septum, hypothalamus, ventral hippocampus, ventral and dorsal mesencephalon. Strong correlations between anxiety-like behavior and ASM activity were found in female HAB rats in the amygdala, ventral hippocampus and dorsal mesencephalon, whereas NSM activity correlated with anxiety levels in the dorsal mesencephalon. These results provide novel information about the sphingolipid metabolism, especially about the sphingomyelinases and ceramidases, in major depression and comorbid anxiety.
Highlights
Major depressive disorder (MDD) is a severe and chronic mood disorder, with a lifetime prevalence of approximately 11% in men and 18% in women [1]
Our study describes for the first time the activity of sphingomyelinases and ceramidases in the
Rats showed increased activity of acid sphingomyelinase (ASM) and neutral sphingomyelinase (NSM) as well as of acid ceramidase (AC) and neutral ceramidase (NC) in multiple brain regions associated with anxiety- and depressive-like behavior, including the lateral septum, hypothalamus, ventral hippocampus and ventral and dorsal mesencephalon
Summary
Major depressive disorder (MDD) is a severe and chronic mood disorder, with a lifetime prevalence of approximately 11% in men and 18% in women [1]. We characterized the brain activity of ASM and NSM as well as of AC and NC in an animal model of innate hyper-anxiety and MDD, namely, in Wistar rats selectively bred for extremely high (HAB) versus low (LAB) anxiety-like behavior, based on their performance on the elevated plus maze (EPM) This model is highly relevant for studying the sphingolipid metabolizing enzymes, as HAB rats show an anxious and depressive-like phenotype similar to ASMtg and ASMtgfb mice but not a social anxious phenotype [35,36]. Given that MDD is more prevalent in women [38] and the social anxious phenotype was observed only in female ASMtg [31] and ASMtgfb mice [33], experiments were performed in female HAB and LAB rats
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