黑质升压和弓状核降压效应及二者间的机能联系

本工作用神经元胞体兴奋剂L-谷氨酸钠(Glu)注入箭毒化、人工呼吸大鼠的下丘脑弓状核(AR),引起血压下降,心率减慢;多巴胺(DA)受体激动剂去水吗啡注入AR和Glu注入黑质(SN)均产生升压和加速心率的效应,Glu(i.SN)效应可被DA受体阻断剂氟哌啶醇注入双侧AR阻断;从而证明:(1)AR具有降压、降心率功能;(2)黑质可通过AR内的DA受体对AR降压、降心率效应起抑制作用,而实现其加压、加速心率效应。     

刺激蓝斑对下丘脑弓状核单位放电的影响

本研究室以往工作表明,下丘脑弓状核(ARC)和蓝斑(LC)在痛觉调制和针刺镇痛中具有重要作用。本实验观察刺激 LC 对清醒制动大鼠 ARC 单位放电的影响。ARC 单位对刺激LC 的反应以抑制为主,在38个单位中有23个单位呈现抑制反应。ARC 单位对外周伤害性刺激的反应以兴奋为主,在27个单位中有20个单位呈现兴奋反应。刺激 LC 可以使 ARC 单位的伤害性反应的持续时间明显缩短。α_2受体激动剂(氯压啶)和α_1受体阻断剂(酚苄明)能加快ARC 单位的平均放电频率,而β-受体激动剂(异丙基肾上腺素)和β受体阻断剂(心得安)则无明显影响。这些结果提示 LC 的去甲肾上腺素能神经元对 ARC 神经元的作用是通过α受体实现的。     

Leptin Signaling in the Arcuate Nucleus Reduces Insulin’s Capacity to Suppress Hepatic Glucose Production in Obese Mice

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递增负荷运动对大鼠下丘脑弓状核ACh、DA、NA、AD的影响

目的:在大鼠进行6周递增负荷运动的过程中,获得下丘脑弓状核乙酰胆碱(ACh)、多巴胺(DA)、去甲肾上腺素(NA)、肾上腺素(AD)阳性神经元表达的变化信息,观察其变化特征,探讨其变化规律及相互关系。方法:通过免疫组化技术测定ACh、DA、NA、AD的表达。结果:在一次负荷运动后即刻和恢复期,ACh变化不明显(P>0.05),DA运动后即刻变化不大,运动后3 h下降(P<0.05),NA变化表现不一(P>0.05),AD运动后明显升高且恢复期仍处于较高水平(P<0.05);在6周运动训练过程中,ACh有降低趋势但变化不明显(P>0.05),DA变化不明显(P>0.05),AD先增加而后逐渐回降(P<0.05),NA可能与AD的变化一致。结论:在一次负荷运动中,下丘脑弓状核ACh、NA、AD与运动应激HPA轴的兴奋有密切关系,AD是促进HPA轴兴奋的主要因素之一。在6周运动训练过程中,HPA应激轴的兴奋可能在运动适应初期由NA、AD,后期由ACh起主导作用。     

GLUT2 immunoreactivity in Gomori-positive astrocytes of the hypothalamus.

A specialized subtype of astrocyte, the Gomori-positive (GP) astrocyte, is unusually abundant and prominent in the arcuate nucleus of the hypothalamus. GP astrocytes possess cytoplasmic granules derived from degenerating mitochondria. GP granules are highly stained by Gomori's chrome alum hematoxylin stain, by the Perl's reaction for iron, or by toluidine blue. The source of the oxidative stress causing mitochondrial damage in GP astrocytes is uncertain, but such damage could arise from the oxidative metabolism of glucose transported into astrocytes by high-capacity GLUT2 glucose transporters. In accord with this hypothesis, the reported anatomical distribution of astrocytes staining positively for GLUT2 glucose transporters closely matches that of GP astrocytes. To examine whether or not these two staining procedures detect the same population of astrocytes, immunocytochemistry was performed on semithin sections to detect GLUT2 protein and sections were then stained with toluidine blue to detect GP granules. It was determined that GP astrocytes are frequently immunoreactive for the GLUT2 transporter protein. These data support the possibility that GP astrocytes may have an important influence upon the reactivity of the hypothalamus to glucose and that a specialized glucose metabolism may in part underlie the development of mitochondrial abnormalities in hypothalamic GP astrocytes.     

Hypothalamic lipotoxicity and the metabolic syndrome

Ectopic accumulation of lipids in peripheral tissues, such as pancreatic β cells, liver, heart and skeletal muscle, leads to lipotoxicity, a process that contributes substantially to the pathophysiology of insulin resistance, type 2 diabetes, steatotic liver disease and heart failure. Current evidence has demonstrated that hypothalamic sensing of circulating lipids and modulation of hypothalamic endogenous fatty acid and lipid metabolism are two bona fide mechanisms modulating energy homeostasis at the whole body level. Key enzymes, such as AMP-activated protein kinase (AMPK) and fatty acid synthase (FAS), as well as intermediate metabolites, such as malonyl-CoA and long-chain fatty acids-CoA (LCFAs-CoA), play a major role in this neuronal network, integrating peripheral signals with classical neuropeptide-based mechanisms. However, one key question to be addressed is whether impairment of lipid metabolism and accumulation of specific lipid species in the hypothalamus, leading to lipotoxicity, have deleterious effects on hypothalamic neurons. In this review, we summarize what is known about hypothalamic lipid metabolism with focus on the events associated to lipotoxicity, such as endoplasmic reticulum (ER) stress in the hypothalamus. A better understanding of these molecular mechanisms will help to identify new drug targets for the treatment of obesity and metabolic syndrome.     

下丘脑内侧基底部去传入及内侧前脑束损毁对弓状核单位伤害性反应及电针反应的影响

在67只清醒麻痹的雄性大鼠身上,记录了157个弓状核(ARC)的单位放电。实验分四组:(1)正常对照组;(2)下丘脑内侧基底部(MBH)前去传入组;(3)MBH后去传入组;(4)内侧前脑束(MFB)损毁组。正常对照组ARC 单位的平均自发放电频率为2.03±0.3Hz(n=60),MBH前、后去传入组,ARC单位的平均自发放电频率比正常对照组显著减慢(P<0.01),说明从MBH前、后侧传入ARC的纤维对ARC单位有紧张性的兴奋作用。 在正常对照组,大多数ARC单位都能对隐神经伤害性刺激和电针起反应;但在MBH前去传入组,大多数ARC单位对隐神经伤害性刺激和电针不起反应。说明隐神经伤害性刺激和电针信息是从MBHM侧的神经通路传入ARC的。 在MFB损毁组,ARC单位对伤害性刺激的反应持续时间(2206.9±305.9ms,n=13)比正常对照组(1300.0±190.4ms,n=24)显著延长(P<0.05),说明MFB对ARC单位的伤害性反应有抑制性的调制作用。     

蓝斑核和中缝背核参与电刺激弓状核引起的大鼠胃内压降低的反应

选用 Wistar 大鼠80只。在乌拉坦麻醉下观察了电刺激弓状核对胃内压的影响并初步分析了其作用的中枢途径。结果为:(1)刺激时,胃内压显著降低;(2)分别电解损毁双侧蓝斑核和中缝背核,均可减弱弓状核的这一作用;(3)侧脑室注射纳洛酮不影响弓状核的这一作用。上述结果表明,电刺激弓状核降低胃内压的作用需有蓝斑核和中缝背核参与,而弓状核内富含的β-内啡肽能神经元可能与这一作用无关。     

Pituitary response to growth hormone-releasing factor in rats with functional or anatomical lesions of the central nervous system that inhibit endogenous growth hormone secretion

The pituitary growth hormone (GH) response to the growth hormone-releasing factor, hpGRF-44, was evaluated in male rats with various lesions of the central nervous system. These included an electrical lesion of the ventromedial hypothalamus, a chemical lesion of the arcuate nucleus induced by neonatal treatment with monosodium glutamate, a functional lesion of catecholamine synthesis with alpha-methyl-p-tyrosine or a functional lesion of catecholamine storage with reserpine. The first three lesions appear to partially inhibit normal somatostatin secretion since in every instance hpGRF-44 administration induced a significant increase in plasma GH concentrations. In contrast, reserpine blocked the GH response to hpGRF-44, presumably by stimulating somatostatin secretion. The pituitary GH response to hpGRF-44 in the above described models was enhanced by pretreatment of the rats with antibodies against somatostatin. The pituitary GH response to repeated injections of hpGRF-44 was also evaluated in rats with an anatomical lesion of the arcuate nucleus or a functional lesion of catecholamine synthesis. The maximum GH response did not vary over time to the repeated injections of hpGRF-44 in rats with lesions of the arcuate nucleus; however, interruption of catecholamine synthesis resulted in a significant decrease in the GH response to hpGRF-44 over time.