Restoration of the luteinizing hormone surge in middle-aged female rats by altering the balance of GABA and glutamate transmission in the medial preoptic area.

Restoration of the luteinizing hormone surge in middle-aged female rats by altering the balance of GABA and glutamate transmission in the medial preoptic area.
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DOI:
10.1095/biolreprod.108.069831
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发表时间:
2008-11
影响因子:
3.6
通讯作者:
Etgen AM
Etgen AM
中科院分区:
生物学2区
文献类型:
--
作者:
Neal-Perry GS;Zeevalk GD;Shu J;Etgen AM

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下丘脑谷氨酸和GABA神经传递参与啮齿类动物卵巢激素诱导的GnRH-LH峰我们以前报道,中年大鼠有显着较少的谷氨酸释放在内侧视前区比年轻大鼠的一天的LH激增。本研究验证了这一假设,即延迟和衰减的LH峰在卵巢切除,中年大鼠与卵巢类固醇的结果减少下丘脑谷氨酸和增加GABAA神经传递。微透析结果显示,与年轻大鼠相比,LH峰减弱的中年大鼠内侧视前区细胞外谷氨酸减少,细胞外GABA水平增加。用荷包牡丹碱阻断GABAA受体或用L-反式-吡咯烷-2,4-二羧酸抑制突触谷氨酸再摄取增加了中年大鼠内侧视前区的细胞外Glu,并部分恢复了LH峰振幅,而不改变LH峰的发生。在荷包牡丹碱和L-反式-吡咯烷-2,4-二甲酸联合治疗的中年大鼠中观察到LH峰幅度的完全恢复。这种治疗也恢复了细胞外谷氨酸:GABA的比例在中年大鼠的内侧视前区的年轻大鼠的水平。免疫印迹分析显示,雌二醇和孕酮治疗降低了SLC 32A 1(以前称为囊泡GABA转运体)水平,并增加了SLC 17 A6(以前称为囊泡谷氨酸转运体2)水平在卵巢切除的年轻,但不是中年大鼠的下丘脑前部。这些数据表明,在雌激素正反馈条件下,谷氨酸的可用性降低和GABAA受体的活化增加有助于与年龄相关的LH峰的发作延迟和振幅衰减。
Hypothalamic glutamate and GABA neurotransmission are involved in the ovarian hormone-induced GnRH-LH surge in rodents. We previously reported that middle-aged rats have significantly less glutamate release in the medial preoptic area than young rats on the day of the LH surge. The present study tested the hypothesis that the delayed and attenuated LH surge in ovariohysterectomized, middle-aged rats primed with ovarian steroids results from reduced hypothalamic glutamate and increased GABAA neurotransmission. Microdialysis results show that middle-aged rats with attenuated LH surges had reduced extracellular glutamate and increased extracellular GABA levels in the medial preoptic area compared to young rats. Blocking GABAA receptors with bicuculline or inhibiting synaptic glutamate reuptake with L-trans-pyrrolidine-2,4-dicarboxylic acid increased extracellular Glu in the medial preoptic area and partially restored LH surge amplitude in middle-aged rats without altering LH surge onset. Complete recovery of LH surge amplitude was observed in middle-aged rats treated with the combination of bicuculline and L-trans-pyrrolidine-2,4-dicarboxylic acid. This treatment also restored the extracellular glutamate:GABA ratio in the medial preoptic area of middle-aged rats to the level of young rats. Immunoblot analysis revealed that estradiol and progesterone treatment reduced SLC32A1(formerly known as vesicular GABA transporter) levels and increased SLC17A6 (formerly known as vesicular glutamate transporter 2) levels in the anterior hypothalamus of ovariohysterectomized young but not middle-aged rats. These data suggest that both reduced availability of glutamate and increased activation of GABAA receptors under estrogen positive feedback conditions contribute to the age-related delay in onset and attenuated amplitude of the LH surge.
DOI: 10.1016/s0006-8993(96)00862-1
发表时间: 1996-11-18
期刊: BRAIN RESEARCH
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发表时间: 1983-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
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DOI: 10.1016/0960-0760(92)90436-m
发表时间: 1992-03-01
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DOI: 10.1210/jc.80.12.3537
发表时间: 1995-12-01
影响因子: 5.8
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