Short-term fasting decreases excitatory synaptic inputs to ventromedial tuberoinfundibular dopaminergic neurons and attenuates their activity in male mice.
Short-term fasting decreases excitatory synaptic inputs to ventromedial tuberoinfundibular dopaminergic neurons and attenuates their activity in male mice.
复制标题
短期禁食会减少雄性小鼠腹内侧结节漏斗部多巴胺能神经元的兴奋性突触输入，并减弱其活性。
DOI：
10.1016/j.neulet.2018.02.017
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Akema T.
中科院分区：
文献类型：
--
作者：
Kubota T;Fukushima A;Hagiwara H;Kamiya Y;Furuta M;Miyazaki T;Fujioka H;Fujiwara SE;Funabashi T;Akema T.
下丘脑弓状核（ARC）中的漏斗部多巴胺能（TIDA）神经元在抑制垂体前叶催乳素（PRL）分泌中起作用。PRL参与各种行为，包括进食。因此，我们假设禁食可能会降低TIDA神经元的活性，这可能会改变PRL分泌。然而，TIDA神经元活动的直接检查是困难的。最近，产生了在大鼠酪氨酸羟化酶基因控制下表达绿色荧光蛋白（GFP）的转基因小鼠。我们首先确定背内侧ARC中的GFP是TIDA神经元的可靠标记。然后，我们在GFP标记的TIDA神经元中进行电生理学和免疫细胞化学，以检查不同的饲养条件是否会改变它们的活性。8周龄雄性小鼠喂食或禁食24 h。处死后，我们制备急性分离的脑切片进行全细胞电压钳记录。用荧光显微镜鉴定TIDA神经元。微兴奋性突触后电流（mEPSC）的平均幅度显着降低，在禁食小鼠相比，喂食小鼠，但不同的喂养条件并不影响平均mEPSC的时间间隔。这一结果表明，禁食减少了TIDA神经元的兴奋性突触输入的数量。为了确定兴奋性突触输入的减少是否会导致TIDA神经元活动的减少，我们研究了24小时禁食对ARC中c-Fos表达的影响。我们发现，禁食显着减少Fos阳性TIDA神经元的数量。此外，血清PRL水平显著升高。总之，目前的研究结果表明，短期禁食衰减TIDA神经元的活动。
Tuberoinfundibular dopaminergic (TIDA) neurons in the arcuate nucleus (ARC) of the hypothalamus play a role in inhibiting prolactin (PRL) secretion from the anterior pituitary. PRL is involved in a variety of behaviors, including feeding. Consequently, we hypothesized that fasting might reduce the activity of TIDA neurons, which might alter PRL secretion. However, direct examinations of TIDA neuron activity are difficult. Recently, transgenic mice were generated that expressed green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene. We first determined that GFP in the dorsomedial ARC was a reliable marker of TIDA neurons. Then, we performed electrophysiology and immunocytochemistry in GFP-labeled TIDA neurons to examine whether different feeding conditions could change their activity. Eight-week-old male mice were fed or fasted for 24 h. After sacrifice, we prepared acutely isolated brain slices for conducting whole-cell voltage-clamp recordings. TIDA neurons were identified with fluorescence microscopy. The mean amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced in fasting mice compared to fed mice, but different feeding conditions did not affect the mean mEPSC intervals. This result suggested that fasting reduced the number of excitatory synaptic inputs to TIDA neurons. To determine whether a reduction in excitatory synaptic inputs would cause a reduction in TIDA neuron activity, we examined the effect of 24-h fasting on c-Fos expression in the ARC. We found that fasting significantly reduced the number of Fos-positive TIDA neurons. In addition, serum PRL levels were significantly increased. Taken together, the present findings suggested that short-term fasting attenuated TIDA neuron activity.