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清醒状态下经甘丙肽处理的大鼠和甘丙肽过表达转基因小鼠腹侧海马乙酰胆碱释放的选择性降低。

Selective reduction in ventral hippocampal acetylcholine release in awake galanin-treated rats and galanin-overexpressing transgenic mice.

作者信息

Laplante François, Crawley Jacqueline N, Quirion Rémi

机构信息

Douglas Hospital Research Centre, Department of Pharmacology/Therapeutics and Department of Psychiatry, McGill University, 6875 Boul. LaSalle Verdun, QC, Canada H4H 1R3.

出版信息

Regul Pept. 2004 Oct 15;122(2):91-8. doi: 10.1016/j.regpep.2004.05.022.

Abstract

The neuropeptide galanin is an inhibitory modulator of hippocampal acetylcholine (ACh) release and cognitive functions. Anatomical evidence demonstrated some differences between the dorsal and ventral hippocampi notably in the expression of galanin receptor subtypes, and the neuronal population on which galanin-like immunoreactivity is expressed. This is suggestive of a differential role for this peptide in these two areas of the hippocampal formation. Using in vivo microdialysis, we investigated the role of galanin on ACh release in the dorsal and ventral hippocampi. Two models were studied: galanin-administered rats and transgenic mice over-expressing galanin (GAL-tg). In rats, galanin (2.0 and 10.0 microM) infused locally through the dialysis probe induced a significant decrease in ACh release in the ventral hippocampus, confirming previous findings, while no effect was seen in the dorsal hippocampus. Using the no net flux method, a significant reduction in ACh levels was noted only in the ventral hippocampus of GAL-tg compared to wild-type littermates. These results suggest that excess endogenous galanin can suppress basal ACh release, with anatomical specificity, to the ventral hippocampus. These results are of interest in the context of galanin receptor subtypes in the dorsal and ventral hippocampus, and the differential alterations of hippocampal subregions in neurological diseases such as Alzheimer's dementia.

摘要

神经肽甘丙肽是海马乙酰胆碱(ACh)释放和认知功能的抑制性调节剂。解剖学证据表明,背侧和腹侧海马之间存在一些差异,特别是在甘丙肽受体亚型的表达以及表达甘丙肽样免疫反应性的神经元群体方面。这表明该肽在海马结构的这两个区域中具有不同的作用。我们使用体内微透析技术,研究了甘丙肽对背侧和腹侧海马中ACh释放的作用。研究了两种模型:给予甘丙肽的大鼠和过度表达甘丙肽的转基因小鼠(GAL-tg)。在大鼠中,通过透析探针局部注入甘丙肽(2.0和10.0 microM)可导致腹侧海马中ACh释放显著减少,证实了先前的研究结果,而在背侧海马中未观察到影响。使用无净通量方法,与野生型同窝小鼠相比,仅在GAL-tg的腹侧海马中观察到ACh水平显著降低。这些结果表明,过量的内源性甘丙肽可以以解剖学特异性抑制腹侧海马的基础ACh释放。这些结果对于背侧和腹侧海马中的甘丙肽受体亚型以及神经疾病(如阿尔茨海默病痴呆)中海马亚区域的差异改变具有重要意义。

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