雌雄发育大鼠下丘脑γ -氨基丁酸B受体亚基的表达

María S. Bianchi , Victoria A. Lux-Lantos , Bernhard Bettler , Carlos Libertun
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引用次数: 22

摘要

GABA及其受体在大鼠不同脑区表现出特定的个体成因分布。最近,GABAB受体(GBR)被描述为由GBR1a/b和GBR2亚基形成的异源二聚体。在这里,大鼠GBRs的个体发生和亚基表达模式在两性下丘脑中被确定,下丘脑是一个关键的稳态调节区域。雄性和雌性大鼠分别于1、4、12、20、28、38天及成年时处死,下丘脑切除并冷冻。Western blots分析显示,GBR1和GBR2亚基在雄性和雌性下丘脑膜中从第1天到成年均有表达。在雌性中,GBR1a和GBR1b在新生儿中表达最多,并在成年后表达减少。出生时,GBR1a的表达量明显高于GBR1b,而在38天时,GBR1b的表达量更丰富。在雄性中,GBR1a和GBR1b的表达在幼龄动物中较高,并在第二周龄和第三周龄之间逐渐下降,显示成体水平,而在同种异型之间没有差异。比较不同性别下丘脑中GBR1变异的水平,出生时,GBR1a在雌性中明显更丰富,而在38天时,其在雄性中的表达更高;GBR1b在发育过程中没有性别差异。各年龄段男女下丘脑均检测到GBR2;12天时达到最高水平,38天时达到成虫水平,无性别差异。本文首次报道了雄性和雌性大鼠下丘脑GABAB受体的个体发生,具有特定的亚基和同型表达的发育模式,并存在一定的性别差异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Expression of gamma-aminobutyric acid B receptor subunits in hypothalamus of male and female developing rats

GABA and its receptors show particular ontogenic distributions in different rat brain areas. Recently, GABAB receptors (GBR) have been described to assemble as heterodimers formed by a GBR1a/b and a GBR2 subunit. Here, the ontogeny of rat GBRs and the pattern of subunit expression in both sexes were determined in the hypothalamus, a critical area for homeostatic regulation. Male and female rats were sacrificed at 1, 4, 12, 20, 28, 38 days of life and at adulthood and hypothalami were removed and frozen. Western blots analysis for GBR1 and GBR2 subunits showed that both were expressed in male and female hypothalamic membranes from day 1 to adulthood. In females, both GBR1a and GBR1b were maximally expressed in newborns and decreased towards adulthood. At birth, expression of GBR1a was significantly higher than GBR1b, while at 38 days, GBR1b was more abundant. In males, GBR1a and GBR1b expression was higher in young animals and decreased gradually showing adult levels between the second and third weeks of age without differences between isoforms. Comparing GBR1 variants levels in hypothalamus between sexes, GBR1a was significantly more abundant in females at birth while at 38 days its expression was higher in males; GBR1b showed no sex differences along development. GBR2 was detected in hypothalami of females and males at all ages; maximum levels were observed at 12 days and adult levels were attained at 38 days, without sex differences. This is the first report on the ontogeny of hypothalamic GABAB receptors in male and female rats, with a particular developmental pattern of subunit and isoform expression and presenting some sex differences.

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