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Impact of caudal hindbrain glycogen metabolism on A2 noradrenergic neuron AMPK activation and ventromedial hypothalamic nucleus norepinephrine activity and glucoregulatory neurotransmitter marker protein expression
Neuropeptides ( IF 2.9 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.npep.2020.102055
Ayed A Alshamrani 1 , Khaggeswar Bheemanapally 1 , Mostafa M H Ibrahim 1 , Karen P Briski 1
Affiliation  

The brain glycogen reserve is a source of oxidizable substrate fuel. Lactoprivic-sensitive hindbrain A2 noradrenergic neurons provide crucial metabolic-sensory input to downstream hypothalamic glucose-regulatory structures. Current research examined whether hindbrain glycogen fuel supply impacts A2 energy stability and governance of ventromedial hypothalamic nucleus (VMN) metabolic transmitter signaling. Male rats were injected into the caudal fourth ventricle (CV4) with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) prior to continuous intra-CV4 infusion of L-lactate or vehicle. Lactate reversed DAB suppression of A2 neuron AMPK protein and up-regulated phosphoAMPK profiles. A2 dopamine-β-hydroxylase expression was refractory to DAB, but elevated by DAB/lactate. Lactate normalized A2 estrogen receptor-alpha and GPER proteins and up-regulated estrogen receptor-beta levels in DAB-treated rats. VMN norepinephrine content was decreased by DAB, but partially restored by lactate. DAB caused lactate-reversible or -irreversible augmentation of VMN glycogen phosphorylase-brain (GPbb) and -muscle type (GPmm) variant profiles, and correspondingly up- or down-regulated VMN protein markers of glucose-stimulatory nitrergic and glucose-inhibitory γ-aminobutyric acid transmission. DAB did not alter plasma glucose, but suppressed or elevated circulating glucagon and corticosterone in that order. Results show that diminished hindbrain glycogen breakdown is communicated to the VMN, in part by NE signaling, to up-regulate VMN glycogen breakdown and trigger neurochemical signaling of energy imbalance in that site. DAB effects on GPmm, VMN glycogen content, and counter-regulatory hormone secretion were unabated by lactate infusion, suggesting that aside from substrate fuel provision rate, additional indicators of glycogen metabolism such as turnover rate may be monitored in the hindbrain.

中文翻译:

尾后脑糖原代谢对 A2 去甲肾上腺素能神经元 AMPK 激活和腹内侧下丘脑核去甲肾上腺素活性和葡萄糖调节神经递质标记蛋白表达的影响

脑糖原储备是可氧化底物燃料的来源。Lactoprivic 敏感的后脑 A2 去甲肾上腺素能神经元为下游下丘脑葡萄糖调节结构提供关键的代谢感觉输入。目前的研究检查了后脑糖原燃料供应是否影响 A2 能量稳定性和腹内侧下丘脑核 (VMN) 代谢传递信号的治理。在连续 CV4 内输注 L-乳酸或载体之前,将雄性大鼠用糖原磷酸化酶抑制剂 1,4-双脱氧-1,4-亚氨基-D-阿拉伯糖醇 (DAB) 注射到尾侧第四脑室 (CV4)。乳酸逆转 DAB 抑制 A2 神经元 AMPK 蛋白和上调磷酸 AMPK 谱。A2 多巴胺-β-羟化酶表达对 DAB 无效,但被 DAB/乳酸升高。在 DAB 治疗的大鼠中,乳酸使 A2 雌激素受体-α 和 GPER 蛋白正常化,并上调雌激素受体-β 水平。DAB 会降低 VMN 去甲肾上腺素含量,但乳酸会部分恢复。DAB 引起 VMN 糖原磷酸化酶脑 (GPbb) 和肌肉型 (GPmm) 变异谱的乳酸可逆或不可逆增加,并相应上调或下调葡萄糖刺激性氮能和葡萄糖抑制性 γ- 的 VMN 蛋白标记物氨基丁酸传输。DAB 不改变血浆葡萄糖,但按此顺序抑制或升高循环胰高血糖素和皮质酮。结果表明,减少的后脑糖原分解部分通过 NE 信号传递到 VMN,以上调 VMN 糖原分解并触发该部位能量失衡的神经化学信号传递。
更新日期:2020-08-01
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