Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons (Nat Neurosci, 2008, 11:309-317)

報告日期: 2008/05/30
報告時間: 15:10/16:00
報告學生: 莊佳穎
講評老師: 許桂森
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/970530-1.pdf

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons

 

Alexis M Stranahan1,2, Thiruma VArumugam2,4, Roy G Cutler2, Kim Lee2, Josephine M Egan3 &

Mark P Mattson2

Commentator: 許桂森 老師

Student:      莊佳穎

 

Abstract:

Diabetes has adversely effects on many organ systems including brain. It appears increasing the risk dementia and impairment of the cognitive functions. However, the mechanism(s) responsible for cognitive dysfunction in diabetes remains unknown. Humans with poorly controlled diabetes show hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in elevated circulating cortisol. Recently studies have provided evidence that elevated adrenal glucocorticoids mediate deficits in cognitive function caused by chronic stress. In addition, chronic stress and high corticosterone can impair synaptic plasticity and inhibit adult neurogenesis. Impairment of both synaptic plasticity and adult neurogenesis believed to disruption of learning and memory.

Whether elevated glucocorticoids contribute to the impairment of synaptic plasticity and neurogenesis, and to associated learning and memory deficits?

The authors provide direct evidence of this hypothesis in rodent models of both insulin-resistant and insulin-deficient diabetes. The results showing that negative effects of diabetes on hippocampus-dependent memory and suppression effects on hippocampal progenitor cell proliferation can be reversed by lowering corticosterone in both insulin-resistant and insulin-deficient mice. Further more, high level of corticosterone contributes centrally to learning deficits. These findings support a role for HPA axis hyperactivity in diabetes-induced cognitive impairment.

 

References:

 

Oitzl, M.S., Fluttert, M., Sutanto, W. & de Kloet, E.R. Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats. Eur. J. Neurosci. 10, 3759–3766 (1998).

 

Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP. Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci. 2008 Mar;11(3):309-17. Epub 2008 Feb 17