Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats
| Autor: | Tomomichi Kanabayashi, Toshio Murase, Shozo Kito, Akiko S. Shingo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty endocrine system diseases medicine.medical_treatment Morris water navigation task Hippocampus Insulysin Streptozocin Behavioral Neuroscience Insulin Detemir Internal medicine medicine Insulin-degrading enzyme Animals Cognitive decline Rats Wistar Maze Learning Protein kinase B Insulin detemir Injections Intraventricular Amyloid beta-Peptides biology business.industry Insulin nutritional and metabolic diseases Streptozotocin Receptor Insulin Rats Insulin Long-Acting Insulin receptor Disease Models Animal Endocrinology biology.protein business Cognition Disorders Somatostatin Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Behavioural brain research. 241 |
| ISSN: | 1872-7549 |
| Popis: | We previously demonstrated that intracerebroventricular streptozotocin (STZ-icv) injection induced cognitive dysfunction and led to decreased expression levels of phospho-cyclic AMP responsive element binding protein (pCREB), Akt, and insulin degrading enzyme (IDE) and increased amyloid beta (Ab) deposition in the hippocampus. In the present study, we aimed to investigate whether treatment with an insulin analogue could prevent STZ-induced cognitive decline by reducing or eliminating these changes in the hippocampus. To test this hypothesis, we administrated a long-acting insulin analogue, detemir, into the third ventricle (3V) of STZ-treated rats and assessed cognitive outcomes using the Morris water maze (MWM), immunohistochemistry, and Golgi-Cox staining. Insulin injection successfully rescued STZ-induced cognitive decline, as evidenced by a marked elevation in learning ability. Detemir treatment also resulted in changes in hippocampal levels of IDE, insulin receptor (IR), Akt, somatostatin (SST), and Ab. The STZ-induced decrease of granule cell layer neurons was also recovered by detemir administration. These results provide evidence that 'brain diabetes' and Alzheimer-type dementia involve similar mechanisms and show that insulin may be a promising therapeutic agent to attenuate cognitive decline. |
| Databáze: | OpenAIRE |
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