School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA 71201, USA.
Int J Mol Sci. 2020 Mar 16;21(6):2013. doi: 10.3390/ijms21062013.
The mediobasal hypothalamus (MBH) shapes the neural regulation of glucostasis by 5'-AMP-activated protein kinase (AMPK)-dependent mechanisms. Yet, the neurochemical identity and neuroanatomical distribution of MBH neurons that express glucoprivic-sensitive AMPK remain unclear. The neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) act within the MBH to correspondingly inhibit or stimulate glucose counter-regulation. The current review highlights recent findings that GABA and NO, neurons located in the ventromedial hypothalamic nucleus (VMN), a distinct important element of the MBH, are direct targets of noradrenergic regulatory signaling, and thereby, likely operate under the control of hindbrain metabolic-sensory neurons. The ovarian hormone estradiol acts within the VMN to govern energy homeostasis. Discussed here is current evidence that estradiol regulates GABA and NO nerve cell receptivity to norepinephrine and moreover, controls the noradrenergic regulation of AMPK activity in each cell type. Future gains in insight on mechanisms underpinning estradiol's impact on neurotransmitter communication between the hindbrain and hypothalamic AMPKergic neurons are expected to disclose viable new molecular targets for the therapeutic simulation of hormonal enhancement of neuro-metabolic stability during circumstances of diminished endogenous estrogen secretion or glucose dysregulation.
中脑基底部（MBH）通过 5'-AMP 激活的蛋白激酶（AMPK）依赖机制塑造葡萄糖稳态的神经调节。然而，表达糖饥饿敏感的 AMPK 的 MBH 神经元的神经化学特性和神经解剖分布尚不清楚。神经递质γ-氨基丁酸（GABA）和一氧化氮（NO）在 MBH 中起作用，相应地抑制或刺激葡萄糖的反向调节。本综述强调了最近的发现，即位于腹内侧下丘脑核（VMN）中的 GABA 和 NO 神经元是去甲肾上腺素调节信号的直接靶标，因此，它们可能受后脑代谢感觉神经元的控制。卵巢激素雌二醇在 VMN 中发挥作用以调节能量稳态。本文讨论了目前的证据表明，雌二醇调节 GABA 和 NO 神经元对去甲肾上腺素的神经细胞接受性，并且控制每个细胞类型中 AMPK 活性的去甲肾上腺素调节。对雌二醇对后脑和下丘脑 AMPK 能神经元之间神经递质通讯影响的机制的进一步深入了解，有望揭示可行的新分子靶点，用于在内源性雌激素分泌减少或葡萄糖失调的情况下，模拟激素增强神经代谢稳定性的治疗。
