title: 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.
abstract: 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.
authors.affiliation: Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: L M
authors.initials: LM
authors.lastname: Yang
authors.forename: X D
authors.initials: XD
authors.lastname: Pan
authors.forename: N
authors.initials: N
authors.lastname: Lin
authors.forename: X C
authors.initials: XC
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011301:Preoptic Area / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016704:Synapsins / Q000378:metabolism*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D016760:Proto-Oncogene Proteins c-fos; D016704:Synapsins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter; D007987:Gonadotropin-Releasing Hormone
keywords: GnRH; VGAT; VGLUT2; ageing; synapsin I