AGE- AND GENDER-RELATED DIFFERENCES IN GABAA RECEPTOR-MEDIATED POSTSYNAPTIC CURRENTS IN GABAergic NEURONS OF THE SUBSTANTIA NIGRA RETICULATA IN THE RAT
AGE- AND GENDER-RELATED DIFFERENCES IN GABAA RECEPTOR-MEDIATED POSTSYNAPTIC CURRENTS IN GABAergic NEURONS OF THE SUBSTANTIA NIGRA RETICULATA IN THE RAT
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DOI：
10.1016/j.neuroscience.2009.06.025
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发表时间：
2009-09-29
期刊：
影响因子：
3.3
通讯作者：
Galanopoulou, A. S.
中科院分区：
文献类型：
--
作者：
Chudomel, O.;Herman, H.;Galanopoulou, A. S.
大鼠黑质前部(SNR)GABA能神经元对GABA(A)能药物的反应性随年龄和性别的变化而改变，从而改变其在癫痫控制中的作用。为了确定自发GABA(A)Rs介导的抑制性突触后电流(SIPSCs)特性的成熟和性别差异是否是这些事件的基础，我们研究了基线和在出生后5-9天、PN12-15和PN28-32应用α1 GABA(A)Rs亚单位选择性激动剂唑吡坦后的sIPSCs。结果与PN5、PN15和PN30处的α1和α3 GABA(A)Rs亚单位免疫反应性(-ir)相关。平均频率、幅度和电荷转移均随年龄增长而增加，10~90%的上升时间和衰减时间随年龄增长而加快。老年大鼠较快的sIPSC动力学与α1-ir升高和α3-ir降低相平行。在PN5-9，男性的SIPSCs(频率、幅度、每个事件携带的电荷和电荷转移)比女性更健壮。在PN28-32，雄性比雌性表现出更高的波幅和更快的运动速度。唑吡坦引起的衰减时间、幅度、电荷转移和α1-ir表达的增加在PN5-9男性中最低，但在两性中随着年龄的增长而增加。我们的研究结果表明，GABA(A)Rs亚单位表达的变化部分是SNR神经元年龄和性别特异性sIPSC变化的基础。然而，观察到sIPSC动力学上的性别差异不能归因于骨周α1表达的变化，表明在大鼠SNR中存在其他性别特有的控制sIPSC动力学的因素。(C)2009年IBRO。爱思唯尔有限公司出版。保留所有权利。
The responsiveness of the rat anterior substantia nigra pars reticulata (SNR) GABAergic neurons to GABA(A)ergic drugs changes with age and gender, altering its role in seizure control. To determine whether maturational and gender-specific differences in the properties of spontaneous GABA(A)Rs-mediated inhibitory postsynaptic currents (sIPSCs) underlie these events, we studied sIPSCs at baseline and after application of the alpha 1 GABA(A)Rs subunit selective agonist zolpidem, at postnatal days (PN) 5-9, PN12-15, and PN28-32. Results were correlated with the alpha 1 and alpha 3 GABA(A)Rs subunit immunoreactivity (-ir) at PN5, PN15, and PN30, using immunochemistry. The mean frequency, amplitude and charge transfer increased whereas the 10-90% rise time and decay time accelerated with age in both genders. The faster sIPSC kinetics in older rats were paralleled by increased alpha 1-ir and decreased alpha 3-ir. At PN5-9, males had more robust sIPSCs (frequency, amplitude, charge carried per event and charge transfer) than females. At PN28-32, males exhibited higher amplitudes and faster kinetics than females. The zolpidem-induced increase of decay times, amplitude and charge transfer and alpha 1-ir expression were the lowest in PN5-9 males but increased with age, in both genders. Our findings demonstrate that alterations in GABA(A)Rs subunit expression partially underlie age- and gender-specific sIPSC changes in SNR neurons. However, the observation of gender differences in sIPSC kinetics that cannot be attributed to changes in perisomatic alpha 1 expression suggests the existence of additional gender-specific factors that control the sIPSC kinetics in rat SNR. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.