Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons.
Electrophysiological Effects of Ghrelin in the Hypothalamic Paraventricular Nucleus Neurons.
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DOI：
10.3389/fncel.2018.00275
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发表时间：
2018
影响因子：
5.3
通讯作者：
Mecawi AS
中科院分区：
文献类型：
--
作者：
Dos-Santos RC;Grover HM;Reis LC;Ferguson AV;Mecawi AS
室旁核（PVN）参与交感神经张力的控制和激素的分泌，已知这两种功能都受ghrelin的影响，这表明ghrelin在该核中的直接作用。然而，ghrelin对不同PVN神经元群体兴奋性的影响尚未得到证实。本研究评估了ghrelin对PVN神经元活性的影响，将反应与PVN神经元亚群相关联。我们使用了64多电极阵列，以研究生长激素释放肽管理对PVN神经元细胞外锋电位频率的影响，记录在从雄性Sprague-Dawley大鼠脑切片。水浴给药10 nM ghrelin增加（29/97，30%）或减少（37/97，38%）PVN神经元的尖峰频率。GABAA和谷氨酸受体拮抗剂消除了峰频率的降低，而没有改变由ghrelin引起的峰频率增加的比例（23/53，43%）。结果表明ghrelin增加PVN神经元活动的直接作用和减少PVN神经元活动的突触依赖性作用。膜片钳记录显示受10 nM ghrelin影响的PVN神经元比例相似（33/95，35%去极化; 29/95，30%超极化）。使用电生理指纹来识别PVN神经元的特定亚群，我们观察到大多数前自主神经元（11/18 - 61%）被ghrelin去极化，而神经内分泌（29%去极化，40%超极化）和大细胞神经元（29%去极化，21%超极化）表现出混合反应。最后，为了将PVN神经元的电生理反应和神经化学表型相关联，记录后收集细胞质，并进行RT-PCR以评估加压素、催产素、促甲状腺激素（TRH）和促肾上腺皮质激素（CRH）释放激素的mRNA的存在。单细胞RT-PCR结果显示，多数TRH和CRH阳性神经元对Ghrelin反应性增强，分别为4/5和3/4。总之，ghrelin直接或间接地增加或降低PVN神经元的活性，这表明ghrelin作用于抑制性PVN神经元，从而降低PVN中表达TRH和CRH的神经元的活性。
The paraventricular nucleus (PVN) is involved in the control of sympathetic tone and the secretion of hormones, both functions known to be influenced by ghrelin, suggesting direct effect of ghrelin in this nucleus. However, the effects of ghrelin on the excitability of different PVN neuronal populations have not been demonstrated. This study assessed the effects of ghrelin on the activity of PVN neurons, correlating the responses to subpopulations of PVN neurons. We used a 64 multielectrode array to examine the effects of ghrelin administration on extracellular spike frequency in PVN neurons recorded in brain slices obtained from male Sprague-Dawley rats. Bath administration of 10 nM ghrelin increased (29/97, 30%) or decreased (37/97, 38%) spike frequency in PVN neurons. The GABAA and glutamate receptors antagonists abolish the decrease in spike frequency, without changes in the proportion of increases in spike frequency (23/53, 43%) induced by ghrelin. The results indicate a direct effect of ghrelin increasing PVN neurons activity and a synaptic dependent effect decreasing PVN neurons activity. The patch clamp recordings showed similar proportions of PVN neurons influenced by 10 nM ghrelin (33/95, 35% depolarized; 29/95, 30% hyperpolarized). Using electrophysiological fingerprints to identify specific subpopulations of PVN neurons we observed that the majority of pre-autonomic neurons (11/18 -61%) were depolarized by ghrelin, while both neuroendocrine (29% depolarizations, 40% hyperpolarizations), and magnocellular neurons (29% depolarizations, 21% hyperpolarizations) showed mixed responses. Finally, to correlate the electrophysiological response and the neurochemical phenotype of PVN neurons, cell cytoplasm was collected after recordings and RT-PCR performed to assess the presence of mRNA for vasopressin, oxytocin, thyrotropin (TRH) and corticotropin (CRH) releasing hormones. The single-cell RT-PCR showed that most TRH-expressing (4/5) and CRH-expressing (3/4) neurons are hyperpolarized in response to ghrelin. In conclusion, ghrelin either directly increases or indirectly decreases the activity of PVN neurons, this suggests that ghrelin acts on inhibitory PVN neurons that, in turn, decrease the activity of TRH-expressing and CRH-expressing neurons in the PVN.
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影响因子：
16.2
作者：
Cowley, MA;Smith, RG;Horvath, TL
通讯作者：
Horvath, TL
影响因子：
2.9
作者：
Jia, Yousheng;Nguyen, Tri;Ross, Michael G.
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Ross, Michael G.
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2.9
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Perello M
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作者：
Guo, FF;Bakal, K;Hollenberg, AN
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Hollenberg, AN