Physiological functions of glucose-inhibited neurones.
Physiological functions of glucose-inhibited neurones.
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DOI：
10.1111/j.1748-1716.2008.01922.x
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
González JA
中科院分区：
文献类型：
--
作者：
Burdakov D;González JA
葡萄糖抑制神经元是调节认知唤醒、体重和重要适应性行为的神经回路的组成部分。它们的放电被细胞外葡萄糖通过我们知之甚少的信号级联直接抑制，最终导致突触后 K+ 或可能的 Cl− 通道的打开。在哺乳动物大脑中，目前对两类葡萄糖抑制神经元了解得最好：表达肽递质 NPY 和刺鼠相关肽 (AgRP) 的下丘脑弓状核 (ARC) 神经元，以及表达肽递质食欲素/下丘脑分泌素的下丘脑外侧 (LH) 神经元。 ARC NPY/AgRP神经元的活性促进食物摄入并抑制能量消耗，它们的破坏导致食物摄入和体重严重减少。 ARC NPY/AgRP 细胞的生理作用是通过投射到许多下丘脑区域以及下丘脑外部位（例如丘脑和腹侧被盖区）来介导的。 LH 的食欲素/下丘脑分泌素神经元对于正常觉醒、能量消耗和奖励寻求至关重要，它们的破坏会导致发作性睡病。食欲素的作用是通过高度广泛的中枢投射介导的，几乎遍及除小脑之外的所有大脑区域，包括大脑皮层的单突触神经支配和自主神经节前神经元。在那里，食欲素作用于两种通常与神经元兴奋相关的特定 G 蛋白偶联受体。除了感知血糖水平的生理变化外，NPY/AgRP 和食欲素神经元的放电都受到“饱腹感”激素瘦素的抑制，并受到“饥饿”激素生长素释放肽的刺激。因此，葡萄糖抑制神经元能够很好地根据能量水平协调不同的大脑状态和行为。
Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K+ or possibly Cl− channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the ‘satiety’ hormone leptin and stimulated by the ‘hunger’ hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels.
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影响因子：
16.2
作者：
Borgland, SL;Taha, SA;Bonci, A
通讯作者：
Bonci, A
DOI：
10.1073/pnas.0507480102
发表时间：
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影响因子：
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作者：
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