Fibroblast Growth Factor 19 Increases the Excitability of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice.
Fibroblast Growth Factor 19 Increases the Excitability of Pre-Motor Glutamatergic Dorsal Vagal Complex Neurons From Hyperglycemic Mice.
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DOI：
10.3389/fendo.2021.765359
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发表时间：
2021
影响因子：
5.2
通讯作者：
Smith BN
中科院分区：
文献类型：
--
作者：
Wean JB;Smith BN
在高血糖小鼠脑室内给药成纤维细胞生长因子19 （FGF19）对后脑产生有效的降糖作用，可能是通过迷走神经副交感神经机制介导的。FGF19增加了高血糖小鼠迷走神经背运动核（DMV）副交感运动神经元的突触兴奋性，但这种突触输入的来源尚不清楚。后脑区（AP）和孤束核（NTS）的神经元表达高水平的FGF受体，并对DMV施加谷氨酸能控制。本研究验证了FGF19通过增加高血糖小鼠谷氨酸能AP和NTS神经元的活性来增加DMV中谷氨酸释放的假设。谷氨酸光激活实验证实，FGF19增加了高血糖小鼠连接DMV的AP和NTS神经元的突触谷氨酸释放，而不是正常血糖小鼠。与预期相反，FGF19对NTS内在膜特性产生了混合作用，并有抑制的趋势，这表明另一种机制负责观察到DMV中谷氨酸释放的影响。与假设一致，FGF19仅在高血糖小鼠的NTS中增加动作电位依赖性谷氨酸释放。最后，谷氨酸光激活实验证实，FGF19增加了高血糖小鼠投射到NTS的谷氨酸能AP神经元的活性。总之，这些结果支持了FGF19增加高血糖小鼠AP和NTS神经元的谷氨酸释放的假设，这些神经元投射到DMV。因此，FGF19在几个点上改变局部迷走-迷走反射回路。此外，由于AP和NTS与大脑中其他几个代谢调节核通信，后脑中的FGF19除了改变副交感神经输出外，还可能改变代谢的神经内分泌和行为方面。
Intracerebroventricular administration of the protein hormone fibroblast growth factor 19 (FGF19) to the hindbrain produces potent antidiabetic effects in hyperglycemic mice that are likely mediated through a vagal parasympathetic mechanism. FGF19 increases the synaptic excitability of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) from hyperglycemic, but not normoglycemic, mice but the source of this synaptic input is unknown. Neurons in the area postrema (AP) and nucleus tractus solitarius (NTS) express high levels of FGF receptors and exert glutamatergic control over the DMV. This study tested the hypothesis that FGF19 increases glutamate release in the DMV by increasing the activity of glutamatergic AP and NTS neurons in hyperglycemic mice. Glutamate photoactivation experiments confirmed that FGF19 increases synaptic glutamate release from AP and NTS neurons that connect to the DMV in hyperglycemic, but not normoglycemic mice. Contrary to expectations, FGF19 produced a mixed effect on intrinsic membrane properties in the NTS with a trend towards inhibition, suggesting that another mechanism was responsible for the observed effects on glutamate release in the DMV. Consistent with the hypothesis, FGF19 increased action potential-dependent glutamate release in the NTS in hyperglycemic mice only. Finally, glutamate photoactivation experiments confirmed that FGF19 increases the activity of glutamatergic AP neurons that project to the NTS in hyperglycemic mice. Together, these results support the hypothesis that FGF19 increases glutamate release from AP and NTS neurons that project to the DMV in hyperglycemic mice. FGF19 therefore modifies the local vago-vagal reflex circuitry at several points. Additionally, since the AP and NTS communicate with several other metabolic regulatory nuclei in the brain, FGF19 in the hindbrain may alter neuroendocrine and behavioral aspects of metabolism, in addition to changes in parasympathetic output.
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