Diabetes exacerbates amyloid and neurovascular pathology in aging‐accelerated mice

Aging Cell

Antonio Currais¹  Marguerite Prior¹  David Lo³  Corinne Jolivalt²  David Schubert¹ 

[1] The Salk Institute for Biological Studies, Laboratory of Cellular Neurobiology, 10010 N. Torrey Pines Rd, La Jolla, CA 92037, USA;University of California San Diego, Department of Pathology, 9500 Gilman Dr., La Jolla, CA 92093, USA;The Salk Institute for Biological Studies, Laboratory of Neuronal Structure and Function, 10010 N. Torrey Pines Rd, La Jolla, CA 92037, USA

关键词: advanced glycation end‐products;    aging;    Alzheimer’s disease;    amyloid angiopathy;    diabetes;    neurovascular inflammation;   

DOI  :  10.1111/acel.12002

来源: Wiley

【 摘 要 】

Summary

Mounting evidence supports a link between diabetes, cognitive dysfunction, and aging. However, the physiological mechanisms by which diabetes impacts brain function and cognition are not fully understood. To determine how diabetes contributes to cognitive dysfunction and age-associated pathology, we used streptozotocin to induce type 1 diabetes (T1D) in senescence-accelerated prone 8 (SAMP8) and senescence-resistant 1 (SAMR1) mice. Contextual fear conditioning demonstrated that T1D resulted in the development of cognitive deficits in SAMR1 mice similar to those seen in age-matched, nondiabetic SAMP8 mice. No further cognitive deficits were observed when the SAMP8 mice were made diabetic. T1D dramatically increased Aβ and glial fibrillary acidic protein immunoreactivity in the hippocampus of SAMP8 mice and to a lesser extent in age-matched SAMR1 mice. Further analysis revealed aggregated Aβ within astrocyte processes surrounding vessels. Western blot analyses from T1D SAMP8 mice showed elevated amyloid precursor protein processing and protein glycation along with increased inflammation. T1D elevated tau phosphorylation in the SAMR1 mice but did not further increase it in the SAMP8 mice where it was already significantly higher. These data suggest that aberrant glucose metabolism potentiates the aging phenotype in old mice and contributes to early stage central nervous system pathology in younger animals.

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland