Age affects spontaneous activity and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons
Age affects spontaneous activity and depolarizing afterpotentials in isolated gonadotropin-releasing hormone neurons
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DOI：
10.1210/en.2008-0308
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Kuehl-Kovarik, M. Cathleen
中科院分区：
文献类型：
--
作者：
Wang, Yong;Garro, Mona;Kuehl-Kovarik, M. Cathleen
脉动性GnRH分泌背后的神经元活动，以及这种活动的内源性产生，仍然知之甚少。很明显，下丘脑水平的变化发生在生殖衰老过程中，但实际上对衰老和生殖后动物的GnRH神经元生理学一无所知。在这些研究中，我们对年轻（3个月）、中年（10个月）和老年（15-18个月）雌性小鼠分离的gnrh增强的绿色荧光蛋白神经元进行了细胞贴壁和全细胞记录。所有小鼠均切除卵巢；其中一半用雌二醇替代。所有年龄段的神经元自发放电，大多数是短脉冲模式，这是GnRH神经元放电的特征。膜的特性不受年龄的影响。然而，年老动物神经元的放电频率显著降低，脉冲模式也明显减少。在老年动物中，200毫秒电流脉冲诱发的去极化后电位的振幅明显较小。此外，雌二醇处理的动物的内向全细胞电流减少，尽管它们不受年龄的显著影响。由于去极化后电位已被证明有助于在非常短暂的兴奋性输入后延长活动放电，因此在老年动物中，去极化后电位的减少可能导致脉冲减弱。此外，频率和模式生成的减少可能导致信息编码不当。因此，衰老过程中GnR神经元的变化可能导致活性失调，可能导致在生殖衰老过渡过程中观察到的LH脉冲减弱。
Neuronal activity underlying the pulsatile secretion of GnRH remains poorly understood, as does the endogenous generation of such activity. It is clear that changes at the level of the hypothalamus are taking place during reproductive aging, yet virtually nothing is known about GnRH neuronal physiology in aging and postreproductive animals. In these studies, we performed cell-attached and whole-cell recordings in GnRH-enhanced green fluorescent protein neurons dissociated from young (3 months), middle-aged (10 months), and old (15-18 months) female mice. All mice were ovariectomized; half were estradiol replaced. Neurons from all ages fired spontaneously, most in a short-burst pattern that is characteristic of GnRH neuronal firing. Membrane characteristics were not affected by age. However, firing frequency was significantly reduced in neurons from old animals, as was spike patterning. The amplitude of the depolarizing afterpotential, evoked by a 200-msec current pulse, was significantly smaller in aged animals. In addition, inward whole-cell currents were reduced in estradiol-treated animals, although they were not significantly affected by age. Because depolarizing after potentials have been shown to contribute to prolonged discharges of activity after a very brief excitatory input, a decreased depolarizing afterpotential could lead to attenuated pulses in older animals. In addition, decreases in frequency and pattern generation could lead to improper information coding. Therefore, changes in the GnR Hneuron during aging could lead to dysregulated activity, potentially resulting in the attenuated LH pulses observed in the transition to reproductive senescence.