Neutral ceramidase is a marker for cognitive performance in rats and monkeys

Abstract

Background Ceramides are lipid molecules determining cell integrity and intercellular signaling, and thus, involved in the pathogenesis of several psychiatric and neurodegenerative disorders. However, little is known about the role of particular enzymes of the ceramide metabolism in the mechanisms of normal behavioral plasticity. Here, we studied the contribution of neutral ceramidase (NC), one of the main enzymes mediating ceramide degradation, in the mechanisms of learning and memory in rats and non-human primates. Methods Naïve Wistar rats and black tufted-ear marmosets (Callithrix penicillata) were tested in several tests for short- and long-term memory and then divided into groups with various memory performance. The activities of NC and acid ceramidase (AC) were measured in these animals. Additionally, anxiety and depression-like behavior and brain levels of monoamines were assessed in the rats. Results We observed a predictive role of NC activity in the blood serum for superior performance of long-term object memory tasks in both species. A brain area analysis suggested that high NC activity in the ventral mesencephalon (VM) predicts better short-term memory performance in rats. High NC activity in the VM was also associated with worse long-term object memory, which might be mediated by an enhanced depression-like state and a monoaminergic imbalance. Conclusions Altogether, these data suggest a role for NC in short- and long-term memory of various mammalian species. Serum activity of NC may possess a predictive role in the assessing the performance of certain types of memory.

COVID-19 and its clinical severity are associated with alterations of plasma sphingolipids and enzyme activities of sphingomyelinase and ceramidase

“…The activity of sphingolipid enzymes was quantified using fluorescent substrates, BODIPY-FL-C12-Sphingomyelin (D-7711, Invitrogen, Carlsbad, CA, USA/Life Technologies, Grand 15 Island, NY, USA) for S-ASM and NSM (Kalinichenko et al 2021a;Kalinichenko et al 2021b) and NBD-C12-ceramide (Cay10007958-1, Cayman Chemical, via Biomol GmbH, Hamburg, Germany) for neutral ceramidase (Kalinichenko et al 2021c) as described previously (Mühle and Kornhuber 2017). Briefly, the reaction was performed in 96 well polystyrene plates with 58 or 50 pmol fluorescently labelled sphingomyelin or Cer, respectively, in a buffer mix totaling 50 µl in volume.…”

Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects

“…However, compensatory changes in the activities of other enzymes of this pathway, particularly ASM or acid and neutral ceramidases, might also be involved in the observed behavioural endophenotype. These enzymes were recently shown to contribute to drug addiction [ 19 , 32 , 57 ], emotional phenotypes [ 8 , 58 ], and cognitive behaviours in rodents [ 42 , 59 ]. However, NSM is the only enzyme of ceramide synthesis and metabolism shown to mediate bone–brain signalling in the co-morbidity trias of alcohol addiction—depression/anxiety—osteoporosis.…”