Omega-3 fatty acid deficiency during perinatal development increases serotonin turnover in the prefrontal cortex and decreases midbrain tryptophan hydroxylase-2 expression in adult female rats: Dissociation from estrogenic effects

被引：63
作者：
McNamara, Robert K. [1 ]
Able, Jessica [1 ]
Liu, Yanhong [1 ]
Jandacek, Ronald [2 ]
Rider, Therese [2 ]
Tso, Patrick [2 ]
Lipton, Jack W. [1 ]
机构：
[1] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Dept Pathol, Cincinnati, OH 45237 USA
来源：
JOURNAL OF PSYCHIATRIC RESEARCH | 2009年 / 43卷 / 06期
关键词：
Omega-3 fatty acids; Docosahexaenoic acid (DHA); 5-HT; 5-HIAA; Estrogen; Prefrontal cortex; Tryptophan hydroxylase-2; Serotonin transporter; 5-HT1A; female; Rat; ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; BLOOD-CELL MEMBRANES; DOCOSAHEXAENOIC ACID; CEREBROSPINAL-FLUID; DEPRESSIVE SYMPTOMS; MAJOR DEPRESSION; FISH CONSUMPTION; MESSENGER-RNA; BRAIN-REGIONS;
D O I：
10.1016/j.jpsychires.2008.09.011
中图分类号：
R749 [精神病学];
学科分类号：
100205 ;
摘要：
A dysregulation in central serotonin neurotransmission and omega-3 fatty acid deficiency have been implicated in the pathophysiology of major depression. To determine the effects of omega-3 fatty acid deficiency on indices of serotonin neurotransmission in the adult rat brain, female rats were fed diets with or without the omega-3 fatty acid precursor alpha-linolenic acid (ALA) during perinatal (E0-P90), post-weaning (P21-P90), and post-pubescent (P60-130) development. Ovariectomized (OVX) rats and OVX rats with cyclic estrogen treatment were also examined. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content, and fatty acid composition were determined in the prefrontal cortex (PFC), and tryptophan hydroxylase-2 (TPH-2), serotonin transporter, and 5-HT1A autoreceptor mRNA expression were determined in the midbrain. ALA deficiency during perinatal (-62%, p = 0.0001), post-weaning (-34%, p = 0.0001), and post-pubertal (-10%, p = 0.0001) development resulted in a graded reduction in adult PFC docosahexaenoic acid (DHA, 22:6n-3) composition. Relative to controls, perinatal DHA-deficient rats exhibited significantly lower PFC 5-HT content (-65%, p = 0.001), significant greater 5-HIAA content (+15%, p = 0.046), and a significant greater 5-HIAA/5-HT ratio (+73%, p = 0.001). Conversely, post-weaning DHA-deficient rats exhibited significantly greater PFC 5-HT content (+12%, p = 0.03), no change in 5-HIAA content, and a significantly smaller 5-HIAA/5-HT ratio (-9%, p = 0.01). Post-pubertal DHA-deficient and OXV rats did not exhibit significant alterations in PFC 5-HT or 5-HIAA content. Only perinatal DHA-deficient rats exhibited a significant reduction in midbrain TPH-2 mRNA expression (-29%, p = 0.03). These preclinical data support a causal link between perinatal omega-3 fatty acid deficiency and reduced central serotonin synthesis in adult female rats that is independent of ovarian hormones including estrogen. (C) 2008 Elsevier Ltd. All rights reserved.
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页码：656 / 663
页数：8
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