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J Neuroendocrinol. 2013 Aug;25(8):753-61. doi: 10.1111/jne.12050.

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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Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.


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 Ca(2+) /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.


GnRH; VGAT; VGLUT2; ageing; synapsin I

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