One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats
One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats
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DOI：
10.1194/jlr.m500362-jlr200
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发表时间：
2006-01-01
影响因子：
6.5
通讯作者：
Rapoport, SI
中科院分区：
文献类型：
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作者：
DeMar, JC;Ma, KZ;Rapoport, SI
断奶时（21 天）的雄性大鼠幼崽接受缺乏或充足的 n-3 多不饱和脂肪酸 (n-3 PUFA) 的饮食，持续 15 周。在接下来的三周内，按顺序测量运动活动、抑郁和攻击性测试的表现，然后测定脑脂质成分。在n-3 PUFA缺乏的大鼠中，与n-3 PUFA充足的大鼠相比，脑磷脂中的二十二碳六烯酸（22:6n-3）减少了36%，二十二碳五烯酸（22:5n-6）升高了90%，而脑磷脂浓度没有变化。缺乏 N-3 PUFA 的大鼠在 Porsolt 强迫游泳抑郁测试中得分显着增加 (P = 0.03)，在隔离诱导的常驻入侵者攻击性测试中阻塞时间 (P = 0.03) 和阻塞次数 (P = 0.04) 得分（多重比较未校正）增加。在抑郁评分和攻击性测试的阻塞时间评分上发现了较大的效应量（d > 0.8）。运动活动的旷场测试得分在各组之间没有显着差异，并且只有小到中等的效应大小。这种单代 n-3 PUFA 剥夺的大鼠模型显示出脑脂质成分以及抑郁和攻击性测试分数的显着变化，可能有助于阐明大脑 PUFA 代谢紊乱对人类抑郁、攻击性和双相情感障碍的影响。
Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (P = 0.03) score on the Porsolt forced-swim test for depression, and increased blocking time (P = 0.03) and blocking number (P = 0.04) scores ( uncorrected for multiple comparisons) on the isolation-induced resident intruder test for aggression. Large effect sizes (d > 0.8) were found on the depression score and on the blocking time score of the aggression test. Scores on the open-field test for locomotor activity did not differ significantly between groups, and had only small to medium effect sizes. This single-generational n-3 PUFA-deprived rat model, which demonstrated significant changes in brain lipid composition and in test scores for depression and aggression, may be useful for elucidating the contribution of disturbed brain PUFA metabolism to human depression, aggression, and bipolar disorder.