Age-related changes in neutral sphingomyelin-specific phospholipase C activity in striatum, hippocampus, and frontal cortex: implication for sensitivity to stress and inflammation.
Previous studies show the enrichment of mammalian brain with neutral sphingomyelin-specific phospholipase C (ceramide-phosphocholine phosphodiesterase, EC 3.1.4.12; N-Sase), a key enzyme of sphingolipid metabolism and sphingolipid-induced signaling.


OBJECTIVE
The objective of this study was to evaluate the membrane-associated and cytosolic N-Sase activities in the brain regions associated with behavior (striatum, hippocampus, and frontal cortex).


RESULTS
Results showed higher membrane-associated N-Sase activity as compared to the N-Sase activity in the cytosolic fractions of all the evaluated brain regions. In the hippocampus, the N-Sase activity was significantly higher than in the striatum and cortex. In addition, age-related changes in the hippocampal N-Sase activities were profoundly higher than in the respective fractions isolated from the striatum and cortex. Age-related decreases in the hippocampal and striatal cytosolic N-Sase activities were accompanied by increases in the membrane N-Sase activities in those brain regions. There was a significant increase in the cortical membrane-associated N-Sase activity with age; however, to a much lesser extend than in other brain regions. The increase in the hippocampal membrane-associated N-Sase activity was accompanied by a higher expression of the inflammatory marker, interleukin-1 beta (IL-1 beta), with age. One of the important findings of the present study is the region-specific expression of heat shock protein 70 (hsp70). Frontal cortex showed lower hsp70 expression in both young and old age groups as compared to the striatal and hippocampal hsp70 levels which can contribute to the recently reported higher cortical sensitivity to oxidative stress.


CONCLUSIONS
In conclusion (a) our results, for the first time to our knowledge, demonstrated the association between the N-Sase activity and the stress/inflammatory markers expression in the brain regions controlling behavior; (b) these findings suggest the role of N-Sase as a contributor to the increased stress and inflammatory sensitivity among the brain regions with age.
Crivello
Natalia A
NA
Nutrition and Neurocognition Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. natalia.crivello@tufts.edu
Rosenberg
Irwin H
IH
Dallal
Gerard E
GE
Bielinski
Donna
D
Joseph
James A
JA
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology / Q000503:physiopathology; D004198:Disease Susceptibility / Q000201:enzymology / Q000503:physiopathology; D004660:Encephalitis / Q000201:enzymology* / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D017397:Prefrontal Cortex / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013312:Stress, Physiological / Q000201:enzymology* / Q000503:physiopathology; D013687:Telencephalon / Q000033:anatomy & histology / Q000201:enzymology* / Q000503:physiopathology; D010738:Type C Phospholipases / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D018836:Inflammation Mediators; D007375:Interleukin-1; D013109:Sphingomyelins; D010738:Type C Phospholipases; C491483:Smpd3 protein, mouse; D013108:Sphingomyelin Phosphodiesterase