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首页> 外文期刊>Journal of neuroendocrinology >Increased vesicular γ-GABA transporter and decreased phosphorylation of synapsin i in the rostral preoptic area is associated with decreased gonadotrophin-releasing hormone and c-fos coexpression in middle-aged female mice
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Increased vesicular γ-GABA transporter and decreased phosphorylation of synapsin i in the rostral preoptic area is associated with decreased gonadotrophin-releasing hormone and c-fos coexpression in middle-aged female mice

机译：视神经前视区水泡γ-GABA转运蛋白增加和突触素i磷酸化降低与中年雌性小鼠促性腺激素释放激素减少和c-fos共表达有关

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Hypothalamic glutamate (Glu) and γ-GABA neurotransmission are involved in the ovarian hormone-induced gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in rodents. Studies have shown that reduced Glu and increased γ-GABA in the rostral preoptic area (rPOA) of the hypothalamus, where most activated GnRH neurones are located, play a key role in decreasing the reproductive function of female rats. However, the mechanism underlying the altered balance of these neurotransmitters is poorly understood. In the present study, we observed a decline in the function of GnRH neurones in the rPOA at the time of the GnRH/LH surge in middle-aged intact female mice with regular oestrous cycles. In young mice, there is an increase of vesicular Glu transporter 2 on the pro-oestrus afternoon, which is not observed in middle-aged mice. By contrast, vesicular γ-GABA transporter levels in young mice decrease at the time of the LH surge, whereas they increase in middle-aged mice. Of note, we found that, in middle-aged mice at the time of the GnRH/LH surge, the phosphorylation of synapsin I at Ser603 and Ca2+/calmodulin-dependent kinase IIα was significantly lower than in young mice. These data suggest that, in middle-aged mice, higher levels of presynaptic stores of GABA, a lack of increase of Glu and a decreased ability of synaptic vesicle mobilisation could account for the imbalance of Glu and GABA in the rPOA, which decreases the activation of GnRH neurones.
机译：下丘脑谷氨酸（Glu）和γ-GABA神经传递与啮齿动物卵巢激素诱导的促性腺激素释放激素（GnRH）/黄体生成激素（LH）激增有关。研究表明，大多数激活的GnRH神经元所在的下丘脑的视前视区（rPOA）中的Glu降低和γ-GABA升高在降低雌性大鼠生殖功能中起着关键作用。然而，对这些神经递质平衡改变的潜在机制了解甚少。在本研究中，我们观察到中年完好的雌性周期周期正常的雌性小鼠在GnRH / LH激增时，rPOA中GnRH神经元的功能下降。在年轻小鼠中，发情前下午水泡Glu转运蛋白2增加，而在中年小鼠中未观察到。相比之下，在LH激增时，幼小小鼠中的囊泡γ-GABA转运蛋白水平降低，而在中年小鼠中则增加。值得注意的是，我们发现，在GnRH / LH激增时的中年小鼠中，Ser603和Ca2 + /钙调蛋白依赖性激酶IIα处突触蛋白I的磷酸化明显低于年轻小鼠。这些数据表明，在中年小鼠中，高水平的突触前GABA储存，缺乏Glu的增加和突触小泡动员能力的下降可能是rPOA中Glu和GABA失衡的原因，这会降低激活GnRH神经元。

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