下丘脑腹内侧核糖调节神经元5'-AMP活化蛋白激酶活性和递质标记蛋白表达的性别二型后脑乳酸调节

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Prabhat R. Napit , Md. Haider Ali , A.S.M. Hasan Mahmood, Mostafa M.H. Ibrahim, Karen P. Briski
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引用次数: 1

摘要

背景可氧化的糖酵解终产物L-乳酸是一种衡量神经细胞代谢燃料稳定性的指标,代谢感觉后脑A2去甲肾上腺素能神经元将其传递给大脑葡萄糖调节网络。目前的研究调查了后脑乳酸缺乏对下丘脑腹内侧核(VMN)葡萄糖调节性氮能和γ-氨基丁酸(GABA)神经元对低血糖的能量传感器和递质标记蛋白反应进行性别特异性控制的前提。方法用激光弹射器显微切割雄性和雌性大鼠VMN皮下注射胰岛素、第四脑室尾侧L-乳酸盐或赋形剂后的一氧化氮合酶(nNOS)或谷氨酸脱羧酶65/67(GAD)免疫反应神经元,进行蛋白质印迹分析。结果后脑乳酸补充逆转了低血糖相关的氮能神经元nNOS表达的增加(男性)或抑制(女性),并阻止了这些神经元中磷酸化AMPK 5’-AMP活化蛋白激酶(pAMPK)表达的上调。在雄性VMN的头冠长度和雌性VMN的中部区域,外源性乳酸盐避免了对GABA能神经元GAD蛋白的低血糖抑制。低血糖雄性(尾侧VMN)和雌性(所有VMN节段)大鼠的乳酸标准化GABA神经元pAMPK图谱。去甲肾上腺素(NE)信号的低血糖模式在整个男性VMN中都是乳酸盐依赖性的,但仅限于嘴侧和女性中间VMN。结论研究结果表明,在每个性别中,区域VMN葡萄糖调节递质对低血糖的反应由后脑乳酸盐状态控制。低血糖相关一氧化氮或GABA释放的后脑代谢感觉调节可能在每个性别的特定VMN头尾节段中涉及AMPK依赖性机制。需要进一步研究后脑对乳糖敏感的VMN神经递质在雄性和雌性大鼠中乳酸盐介导的低血糖高血糖血症和高皮质激素血症的减轻中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sex-dimorphic hindbrain lactate regulation of ventromedial hypothalamic nucleus glucoregulatory neuron 5’-AMP-activated protein kinase activity and transmitter marker protein expression

Background

The oxidizable glycolytic end-product L-lactate is a gauge of nerve cell metabolic fuel stability that metabolic-sensory hindbrain A2 noradrenergic neurons impart to the brain glucose-regulatory network. Current research investigated the premise that hindbrain lactate deficiency exerts sex-specific control of energy sensor and transmitter marker protein responses to hypoglycemia in ventromedial hypothalamic nucleus (VMN) glucose-regulatory nitrergic and γ-aminobutyric acid (GABA) neurons.

Methods

Nitric oxide synthase (nNOS)- or glutamate decarboxylase65/67 (GAD)-immunoreactive neurons were laser-catapult-microdissected from male and female rat VMN after subcutaneous insulin injection and caudal fourth ventricular L-lactate or vehicle infusion for Western blot protein analysis.

Results

Hindbrain lactate repletion reversed hypoglycemia-associated augmentation (males) or inhibition (females) of nitrergic neuron nNOS expression, and prevented up-regulation of phosphorylated AMPK 5’-AMP-activated protein kinase (pAMPK) expression in those neurons. Hypoglycemic suppression of GABAergic neuron GAD protein was averted by exogenous lactate over the rostro-caudal length of the male VMN and in the middle region of the female VMN. Lactate normalized GABA neuron pAMPK profiles in hypoglycemic male (caudal VMN) and female (all VMN segments) rats. Hypoglycemic patterns of norepinephrine (NE) signaling were lactate-dependent throughout the male VMN, but confined to the rostral and middle female VMN.

Conclusions

Results document, in each sex, regional VMN glucose-regulatory transmitter responses to hypoglycemia that are controlled by hindbrain lactate status. Hindbrain metabolic-sensory regulation of hypoglycemia-correlated nitric oxide or GABA release may entail AMPK-dependent mechanisms in specific VMN rostro-caudal segments in each sex. Additional effort is required to examine the role of hindbrain lactoprivic-sensitive VMN neurotransmitters in lactate-mediated attenuation of hypoglycemic hyperglucagonemia and hypercorticosteronemia in male and female rats.

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来源期刊
Neuropeptides
Neuropeptides 医学-内分泌学与代谢
CiteScore
5.40
自引率
6.90%
发文量
55
审稿时长
>12 weeks
期刊介绍: The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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