Skip Navigation


ToxSci Advance Access originally published online on June 5, 2009
Toxicological Sciences 2009 111(1):72-79; doi:10.1093/toxsci/kfp126
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
111/1/72    most recent
kfp126v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Wang, S.-h.
Right arrow Articles by Yang, B.-q.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S.-h.
Right arrow Articles by Yang, B.-q.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Diabetes Impairs Hippocampal Function via Advanced Glycation End Product Mediated New Neuron Generation in Animals with Diabetes-Related Depression

Shao-hua Wang*, Zi-lin Sun*,1, Yi-jing Guo{dagger}, Yang Yuan* and Bing-quan Yang*

* The Department of Endocrinology {dagger} The Department of Neurology, affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China 210009

1 To whom correspondence should be addressed at The Department of Endocrinology, affiliated ZhongDa Hospital of Southeast University, No. 87 DingJiaQiao Road, Nanjing, PR China 210009. Fax: +86-25-83285132. E-mail: sunzilin1963{at}yahoo.com.cn.

Received March 30, 2009; accepted May 21, 2009


  Abstract

The diabetes-induced reduction of neurogenesis in hippocampal dentate and its reversal with antidepressant medications implies a potential mechanism for diabetes-related depression and cognitive decline. In the following article, the role of advanced glycation end products (AGEs) in hippocampal neurogenesis deficits in diabetic animals with depression has been further explained in the light of an in vitro study. Diabetes was induced in animals with the use of streptozotocin (55 mg/kg, i.p.), and the animals then divided into those with and those without depression-like behaviors as analyzed by behavioral tests. The AGE formation inhibitor aminoguanidine (10 mg/kg) was administrated for an additional 4 weeks. Proliferating cells, their survival, and their phenotype fate were monitored with bromodeoxyuridine labeling and confocal laser microscopy. The presence of AGE peptides was determined with the use of a flow injection assay. Animals with diabetes and depressive symptoms displayed a reduction in hippocampal neurogenesis and an elevated serum level of AGE peptides, both of which were reversed by a 4-week regimen of aminoguanidine (10 mg/kg, i.p.), which inhibits AGE formation; in addition, the depressive behaviors were improved. These findings provided in vivo evidence that diabetes impairs hippocampal function via the AGE-mediated generation of new neurons. This likely represents a putative mechanism that is responsible for diabetes-related depression and cognitive decline, and it suggests a potential approach for future research.

Key Words: diabetes mellitus; hippocampus; neurogenesis; advanced glycation end products, neural stem cells; depression.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.