A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia.

A very large number of GABAergic neurons are activated in the tuberal hypothalamus during paradoxical (REM) sleep hypersomnia.
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DOI:
10.1371/journal.pone.0011766
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发表时间:
2010-07-26
期刊:
影响因子:
3.7
通讯作者:
Peyron C
Peyron C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sapin E;Bérod A;Léger L;Herman PA;Luppi PH;Peyron C

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我们最近发现,使用Fos免疫染色,结节和乳头状下丘脑含有大量的神经元,特别是在异相睡眠(PS)嗜睡激活。我们进一步表明,下丘脑结节的一些激活的神经元表达黑色素浓集激素(MCH)神经肽,并且icv注射MCH诱导PS数量的强烈增加。然而,在PS过程中激活的大多数神经元的化学性质尚未得到表征。为了确定这些神经元是否为GABA能神经元,我们将GAD 67 mRNA的原位杂交和Fos的免疫组织化学检测结合在对照组、PS剥夺和PS高睡眠大鼠中。我们发现,74%的非常大的人口的Fos标记的神经元位于结节性下丘脑PS嗜睡后,GAD阳性。结合MCH免疫组化和GAD 67原位杂交,我们进一步证明了85%的MCH神经元也呈GAD阳性。最后,根据三组双染计数的Fos-ir/GAD+、Fos-ir/MCH+和GAD+/MCH+双标神经元的数量,我们发现PS过度睡眠后位于结节下丘脑的大量Fos-ir/GAD+神经元中约80%不含MCH。基于这些和以前的结果,我们建议,非MCH Fos/GABA能神经元群体可能参与PS的诱导和维持,而Fos/MCH/GABA能神经元可能参与PS的稳态调节。需要进一步的调查来证实这一最初的假设。
We recently discovered, using Fos immunostaining, that the tuberal and mammillary hypothalamus contain a massive population of neurons specifically activated during paradoxical sleep (PS) hypersomnia. We further showed that some of the activated neurons of the tuberal hypothalamus express the melanin concentrating hormone (MCH) neuropeptide and that icv injection of MCH induces a strong increase in PS quantity. However, the chemical nature of the majority of the neurons activated during PS had not been characterized. To determine whether these neurons are GABAergic, we combined in situ hybridization of GAD67 mRNA with immunohistochemical detection of Fos in control, PS deprived and PS hypersomniac rats. We found that 74% of the very large population of Fos-labeled neurons located in the tuberal hypothalamus after PS hypersomnia were GAD-positive. We further demonstrated combining MCH immunohistochemistry and GAD67 in situ hybridization that 85% of the MCH neurons were also GAD-positive. Finally, based on the number of Fos-ir/GAD+, Fos-ir/MCH+, and GAD+/MCH+ double-labeled neurons counted from three sets of double-staining, we uncovered that around 80% of the large number of the Fos-ir/GAD+ neurons located in the tuberal hypothalamus after PS hypersomnia do not contain MCH. Based on these and previous results, we propose that the non-MCH Fos/GABAergic neuronal population could be involved in PS induction and maintenance while the Fos/MCH/GABAergic neurons could be involved in the homeostatic regulation of PS. Further investigations will be needed to corroborate this original hypothesis.
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