期刊
JOURNAL OF NEUROENDOCRINOLOGY
卷 25, 期 8, 页码 753-761出版社
WILEY-BLACKWELL
DOI: 10.1111/jne.12050
关键词
ageing; GnRH; VGAT; VGLUT2; synapsin I
资金
- National Key Basic Research Program of China [20070392004]
- Fujian Provincial Department of Education Project [JK2010025]
Hypothalamic glutamate (Glu) and -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 -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 -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 II 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.
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