Lipidomic analyses of the mouse brain after antidepressant treatment: evidence for endogenous release of long-chain fatty acids?
Recently, there has been considerable interest in a possible link between changes in brain polyunsaturated fatty acids, neural membrane phospholipid degradation, serotonergic neurotransmission, and depression. The present study aims to examine effects of antidepressants on lipids in different regions of the brain at individual molecular species level, using the novel technique of lipidomics. Balb/C mice received daily intraperitoneal (i.p.) injections of 10 mg/kg of the antidepressants maprotiline, fluoxetine and paroxetine for 4 wk. The prefrontal cortex, hippocampus, striatum and cerebellum were harvested, and lipid profiles compared to those of saline-injected mice. Treatment with maprotiline and paroxetine, but not fluoxetine, resulted in significant decreases in phosphatidylcholine (PC) species, PC36:1, PC38:3, PC40:2p, PC40:6, PC40:5, PC42:7p, PC42:6p and PC42:5p in the prefrontal neocortex. The decreases in phospholipids were accompanied by increases in lysophospholipid species, lysoPC16:0, lysoPC18:2 and lysoPC18:0 in the prefrontal cortex, indicating increase in phospholipase A2 activity and possible release of long-chain fatty acids. Maprotiline and paroxetine treatment also resulted in decreases in sphingomyelin and increases in several ceramide species in the prefrontal cortex. It is postulated that endogenous release of long-chain fatty acids may be related to the mechanism of action of maprotiline and paroxetine.
Lee
Lynette Hui-Wen
LH
Department of Pharmacology, National University of Singapore, Singapore.
Shui
Guanghou
G
Farooqui
Akhlaq A
AA
Wenk
Markus R
MR
Tan
Chay-Hoon
CH
Ong
Wei-Yi
WY
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000378:metabolism*; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008376:Maprotiline / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017374:Paroxetine / Q000008:administration & dosage / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013109:Sphingomyelins / Q000378:metabolism; D013997:Time Factors
D000928:Antidepressive Agents; D002518:Ceramides; D005227:Fatty Acids; D008246:Lysophospholipids; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D005473:Fluoxetine; D008376:Maprotiline; D017374:Paroxetine; D054467:Phospholipases A2