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Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats.
Behav Brain Res. 2013 Mar 15; 241:105-11.BB

Abstract

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.

Authors+Show Affiliations

Okinaka Memorial Institute for Medical Research, Tokyo, Japan. akisheashin@toranomon.gr.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23238038

Citation

Shingo, Akiko Sheala, et al. "Intracerebroventricular Administration of an Insulin Analogue Recovers STZ-induced Cognitive Decline in Rats." Behavioural Brain Research, vol. 241, 2013, pp. 105-11.
Shingo AS, Kanabayashi T, Kito S, et al. Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behav Brain Res. 2013;241:105-11.
Shingo, A. S., Kanabayashi, T., Kito, S., & Murase, T. (2013). Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. Behavioural Brain Research, 241, 105-11. https://doi.org/10.1016/j.bbr.2012.12.005
Shingo AS, et al. Intracerebroventricular Administration of an Insulin Analogue Recovers STZ-induced Cognitive Decline in Rats. Behav Brain Res. 2013 Mar 15;241:105-11. PubMed PMID: 23238038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intracerebroventricular administration of an insulin analogue recovers STZ-induced cognitive decline in rats. AU - Shingo,Akiko Sheala, AU - Kanabayashi,Tomomichi, AU - Kito,Shozo, AU - Murase,Toshio, Y1 - 2012/12/10/ PY - 2012/09/25/received PY - 2012/11/30/revised PY - 2012/12/04/accepted PY - 2012/12/15/entrez PY - 2012/12/15/pubmed PY - 2013/7/3/medline SP - 105 EP - 11 JF - Behavioural brain research JO - Behav Brain Res VL - 241 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/23238038/Intracerebroventricular_administration_of_an_insulin_analogue_recovers_STZ_induced_cognitive_decline_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00779-6 DB - PRIME DP - Unbound Medicine ER -