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糖尿病对认知的影响:从啮齿动物模型中能学到什么?

The impact of diabetes on cognition: what can be learned from rodent models?

作者信息

Biessels Geert Jan, Gispen Willem Hendrik

机构信息

Department of Neurology, G03.228, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.

出版信息

Neurobiol Aging. 2005 Dec;26 Suppl 1:36-41. doi: 10.1016/j.neurobiolaging.2005.08.015. Epub 2005 Oct 11.

Abstract

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.

摘要

糖尿病与认知功能的轻度损害有关,尤其是在老年人中。此外,患痴呆症的风险会增加。我们在此回顾啮齿动物模型的研究,这些研究可能有助于确定糖尿病对大脑产生这些不利影响的潜在机制。目前在许多此类模型中已发现学习和记忆、突触可塑性以及谷氨酸能神经传递存在异常。一般来说,以慢性高血糖和低胰岛素血症为特征的模型(称为1型糖尿病模型)中的观察结果相当一致,并且这些模型正越来越多地用于研究发病机制和开发新疗法。然而,以胰岛素抵抗、高胰岛素血症和轻度高血糖为特征的模型(称为2型糖尿病模型)的结果则更具变异性。此外,糖尿病与衰老之间可能的相互作用尚未得到充分研究。由于临床上相关的认知缺陷主要发生在老年2型糖尿病患者中,该领域研究人员面临的挑战将是进一步开发合适的模型。

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