Novel neurotransmitters for sleep and energy homeostasis.
Novel neurotransmitters for sleep and energy homeostasis.
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用于睡眠和能量稳态的新型神经递质。
DOI：
10.1007/978-3-540-49421-8_11
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
deLecea,L
中科院分区：
文献类型：
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作者：
Sutcliffe,JG;deLecea,L
我们已经开发了用于鉴定在脑内具有高度限制表达的mRNA的方法。一种出生后发病的mRNA，局限于大脑皮层和海马的稀疏GABA能中间神经元，编码前皮质抑素原，这是一种与生长抑素共享11个氨基酸的14个残基肽的前体。皮质抑素结合所有五个克隆生长抑素受体时，他们在转染细胞中表达和抑制神经元活动，但与生长抑素，它减少运动活动和诱导慢波睡眠。皮质激素抑制素的mRNA在睡眠剥夺期间积累，显然是通过拮抗乙酰胆碱对皮质兴奋性的影响来发挥作用，从而引起同步脑慢波。与生长抑素的一个氨基酸差异解释了两种肽在生理和行为上的显著差异。第二种出生后发病的mRNA，仅限于下丘脑背外侧的1100个大的神经元细胞体，编码前下丘脑泌素原，这是两种肽的前体，这两种肽彼此之间以及与分泌素肽家族的成员具有同源性。这些肽在神经纤维突触的分泌囊泡中被化学检测到，这些纤维投射到下丘脑后部和其他脑区的靶点。当应用于培养的下丘脑神经元时，肽是兴奋性的。Sakurai及其同事（1998）的最新研究已经确定了下丘脑分泌素肽（这些工作者称为食欲素）作为两种孤儿受体的配体，它们刺激食物摄入行为。下丘脑泌素预测表明肽的额外稳态作用。这些研究表明，通过基于转录的肽递质积累来调节必要但自愿的行为（睡眠和进食）的共同机制，这些肽递质为自愿活动创造了压力。
We have developed methodologies for identifying mRNAs with highly restricted expression within the brain. One postnatal-onset mRNA, restricted to sparse GABAergic interneurons of the cerebral cortex and hippocampus, encodes preprocortistatin, the precursor of a 14-residue peptide that shares 11 amino acids with somatostatin. Cortistatin binds to all five cloned somatostatin receptors when they are expressed in transfected cells and depresses neuronal activity, but, unlike somatostatin, it reduces locomotor activity and induces slow-wave sleep. Cortistatin, whose mRNA accumulates during sleep deprivation, apparently acts by antagonizing the effects of acetylcholine on cortical excitability, thereby causing synchronization brain slow waves. A single amino acid difference with somatostatin accounts for the dramatic differences in the effects of the two peptides on physiology and behavior.A Second postnatal-onset MRNA, restricted to 1100 large neuronal cell bodies of the dorsal-lateral hypothalamus, encodes preprohypocretin, the precursor of two peptides that share homology with each other and with membes of the secretin peptide family. The peptides are detected immunohistochemicaly in secretory vesicles at synapse of fibers that project to posterior hypothalamus and divese targets in other brain regions. The peptides are excitatory when applied to cultured hypothalamic neurons. Recent studies by Sakurai and colleagues (1998) have identified the hypocretin peptides (called the orexins by those workers) as ligands for two orphan receptors at which they stimulate food-intake behavior Sakurai and collaborators showed that the mRNA for these peptides accumulates during food deprivation. The hypocretin projections suggest additional homeostatic roles for the peptides. These studies suggest the common mechanism of regulation for necessary, but voluntary, behaviors (sleep and feeding) by transcription-based accumulation of peptide transmitters that create a pressure for the voluntary activities.