Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior
Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior
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DOI：
10.1073/pnas.1005003107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
McCarthy, Margaret M.
中科院分区：
文献类型：
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作者：
Krebs-Kraft, Desiree L.;Hill, Matthew N.;McCarthy, Margaret M.
杏仁核是一个两性异形的大脑区域，对社会、认知和情感行为的调节至关重要，但杏仁核中性别差异的性质和来源在很大程度上是未知的。我们已经确定了一个独特的性别差异，在发展中的大鼠内侧杏仁核（MeA）的大麻素调节。新生女性的细胞增殖率高于男性。用大麻素受体激动剂WIN 55，212-2（WIN）治疗新生儿，将雌性的细胞增殖降低至雄性，并且宽范围的WIN剂量对雄性的细胞增殖没有影响。WIN对MeA中细胞增殖的影响被CB 2而不是CB 1受体拮抗剂的共同输注所阻止。女性有较高的杏仁核含量的内源性大麻素降解酶，脂肪酸酰胺水解酶，和单酰基甘油脂肪酶比男性，和较低的内源性大麻素2-花生四烯酸甘油和N-花生四烯酸乙醇酰胺（anandamide）。抑制2-花生四烯酰甘油在女性中的降解闭塞细胞增殖的性别差异。细胞命运的分析表明，女性有显着更多的新生成的神经胶质细胞，但没有更多的新生成的神经元比男性，与WIN治疗显着降低了女性的神经胶质细胞的生成，但不是男性。最后，早期暴露于大麻素男性化的青少年玩行为的女性，但并没有改变这种行为的男性。总的来说，我们的研究结果表明，内源性大麻素的性别差异介导了胶质细胞发生的性别差异，在发展中的MeA，影响青春期的性别特异性行为。
The amygdala is a sexually dimorphic brain region critical for the regulation of social, cognitive, and emotional behaviors, but both the nature and the source of sex differences in the amygdala are largely unknown. We have identified a unique sex difference in the developing rat medial amygdala (MeA) that is regulated by cannabinoids. Newborn females had higher rates of cell proliferation than males. Treatment of neonates with the cannabinoid receptor agonist, WIN55,212-2 (WIN), reduced cell proliferation in females to that of males and a wide range of WIN doses had no effect on cell proliferation in males. The effect of WIN on cell proliferation in the MeA was prevented by coinfusions of a CB2 but not CB1 receptor antagonist. Females had higher amygdala content of the endocannabinoid degradation enzymes, fatty acid amid hydrolase, and monoacylglycerol lipase than males, and lower amounts of the endocannabinoids 2-arachidonoylglycerol and N-arachidonylethanolamide (anandamide). Inhibition of the degradation of 2-arachidonoylglycerol in females occluded the sex difference in cell proliferation. Analyses of cell fate revealed that females had significantly more newly generated glial cells but not more newly generated neurons than males, and treatment with WIN significantly decreased glial cell genesis in females but not males. Finally, early exposure to cannabinoids masculinized juvenile play behavior in females but did not alter this behavior in males. Collectively, our findings suggest that sex differences in endocannabinoids mediate a sex difference in glial cell genesis in the developing MeA that impacts sex-specific behaviors in adolescence.