Direct regulation of adult brain function by the male-specific factor SRY
Direct regulation of adult brain function by the male-specific factor SRY
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DOI：
10.1016/j.cub.2006.01.017
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发表时间：
2006-02-21
期刊：
影响因子：
9.2
通讯作者：
Vilain, E
中科院分区：
文献类型：
--
作者：
Dewing, P;Chiang, CWK;Vilain, E
哺乳动物大脑性别分化的中心教条认为，性腺来源的性类固醇组织了发育中大脑的神经回路[1]。最近的证据已经开始挑战这一观点，并表明，与性腺分泌物的男性化作用无关，XY和XX脑细胞有不同的基因表达模式，影响它们的分化和功能[2]。我们之前已经证明，在发育中的男性和女性大脑中存在特定的基因表达差异，而且这些差异先于性腺激素的影响[3]。在这里，我们证明了Y染色体连锁的雄性决定基因Sty在成年雄性啮齿动物的黑质酪氨酸羟基酶表达神经元中特异表达。此外，使用反义寡核苷酸，我们发现黑质Sry下调导致酪氨酸羟化酶表达的统计显著降低，而对神经元数量没有总体影响，这种减少导致雄性大鼠运动障碍。我们的研究表明，Sty直接影响黑质纹状体系统多巴胺能神经元的生化特性及其控制的特定运动行为。这些结果表明，只在男性基因组中编码的基因对大脑产生了直接的男性特异性影响，而没有任何性腺激素的调节。
The central dogma of mammalian brain sexual differentiation has contended that sex steroids of gonadal origin organize the neural circuits of the developing brain [1]. Recent evidence has begun to challenge this idea and has suggested that, independent of the masculinizing effects of gonadal secretions, XY and XX brain cells have different patterns of gene expression that influence their differentiation and function [2]. We have previously shown that specific differences in gene expression exist between male and female developing brains and that these differences precede the influences of gonadal hormones [3]. Here we demonstrate that the Y chromosome-linked, male-determining gene Sty is specifically expressed in the substantia nigral of the adult male rodent in tyrosine hydroxylase-expressing neurons. Furthermore, using antisense oligodeoxynucleotides, we show that Sry downregulation in the substantia nigra causes a statistically significant decrease in tyrosine hydroxylase expression with no overall effect on neuronal numbers and that this decrease leads to motor deficits in male rats. Our studies suggest that Sty directly affects the biochemical properties of the dopaminergic neurons of the nigrostriatal system and the specific motor behaviors they control. These results demonstrate a direct male-specific effect on the brain by a gene encoded only in the male genome, without any mediation by gonadal hormones.