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Pathobiology of Diabetic Encephalopathy in Animal Models

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Diabetes and the Brain

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

This review will compare longitudinally the cognitive deficits and associated metabolic and structural abnormalities in two models with spontaneous onset of type 1 and type 2 diabetes, respectively. From these studies it is becoming increasingly evident that the cerebral dysmetabolism differs in many respects as to underlying mechanisms leading up to progressive cognitive dysfunction, although mechanistic overlaps exist between the two models. In the type 1 model, insulin deficiency appears to play a prominent role in degenerative and apoptotic phenomena of neuronal populations and white matter constituents. In these processes, undoubtedly, hyperglycemia and its downstream metabolic aberrations are also active participants.

In the type 2 model, which reflects closely the situation in human type 2 diabetes, the underlying mechanisms appear more complex and are likely to include components of the metabolic syndrome such as hypercholesterolemia and hypertension. This model displays increased activity of the amyloidogenic processing of APP with subsequent accumulation of A(amyloid)β products. This together with central insulin resistance is likely to be responsible for increased presence of hyperphosphorylated tau. Hence, in this model similarities with factors responsible for the progressive degenerative changes characterizing Alzheimer’s disease are obvious. Although information to date is rather limited in genetically unmanipulated models of diabetes, available information stresses differences in the pathogeneses responsible for diabetic encephalopathy in the two types of diabetes will be reviewed.

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Authors and Affiliations

  1. Department of Pathology, Wayne State University School of Medicine, 48201, Detroit, MI, USA

    Anders A.F. Sima

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  1. Anders A.F. Sima
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Correspondence to Anders A.F. Sima .

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  1. Dept. Neurology, University Medical Center Utrecht, Utrecht, 3508 GA, Netherlands

    Geert Jan Biessels

  2. Medical Center, Columbia University, West 168th St. 622, New York, 10032, U.S.A.

    Jose A. Luchsinger

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Sima, A.A. (2009). Pathobiology of Diabetic Encephalopathy in Animal Models. In: Biessels, G., Luchsinger, J. (eds) Diabetes and the Brain. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-60327-850-8_17

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  • DOI: https://doi.org/10.1007/978-1-60327-850-8_17

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