期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 12, 期 7, 页码 953-964出版社
OXFORD UNIV PRESS
DOI: 10.1017/S146114570900995X
关键词
Antidepressants; fatty acids; lipidomics
资金
- Singapore National Research Foundation under CRP Award [2007-04]
- Academic Research Fund [R-183-000-160-112]
- Biomedical Research Council of Singapore [R-183-000-211-305]
- National Medical Research Council [R-183-000-224-213]
Recently, there has been considerable interest ill 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 A(2) activity and possible release of long-chain fatty acids. Maprotiline and paroxetine treatment also resulted in decreases in sphingomyelin and increases in several cerarnicle 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.
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