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Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model.
J Neural Transm (Vienna) 2012; 119(11):1407-16JN

Abstract

Brain metabolic dysregulation is a hallmark pathological change in Alzheimer's disease (AD). Although detailed mechanisms are still not fully elucidated, recent studies suggest alterations of insulin-signaling transduction cascades underlie neuronal stresses in AD brains. In this study, we performed in vivo experiments to determine the impact of soluble Aβ oligomers on insulin-signaling transduction in rat hippocampi by utilizing lateral ventricular injection of amyloid beta (Aβ) oligomers on male Wistar rats (225 ± 25 g, 3-4 months old) as an AD rat model. The Aβ-infused rats manifested remarkably increased escape latency and significantly decreased proportions of time and pathway crossing the hidden platform as compared to the rats in the pseudo-injection group and the non-injection group in Morris water maze test implicating the damaging effect of soluble Aβ oligomers on rat learning and memory functions. Accordingly, our subsequent results demonstrated that the infusion of soluble Aβ oligomers significantly decreased the expressions of insulin receptor, insulin receptor substrate-I, B cell lymphoma/leukemia-2 and serine/threonine protein kinase B in rat hippocampal neurons, whereas the expression level of total cAMP response element-binding protein was not changed. This study suggests that soluble Aβ oligomers instigated insulin-signaling disturbances which are potentially associated with learning and memory deficits in the AD rat model.

Authors+Show Affiliations

Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324# Jingwu Weiqi Road, Jinan 250021, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

22527777

Citation

Han, Xiaojuan, et al. "Changes in Insulin-signaling Transduction Pathway Underlie Learning/memory Deficits in an Alzheimer's Disease Rat Model." Journal of Neural Transmission (Vienna, Austria : 1996), vol. 119, no. 11, 2012, pp. 1407-16.
Han X, Ma Y, Liu X, et al. Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model. J Neural Transm (Vienna). 2012;119(11):1407-16.
Han, X., Ma, Y., Liu, X., Wang, L., Qi, S., Zhang, Q., & Du, Y. (2012). Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model. Journal of Neural Transmission (Vienna, Austria : 1996), 119(11), pp. 1407-16. doi:10.1007/s00702-012-0803-1.
Han X, et al. Changes in Insulin-signaling Transduction Pathway Underlie Learning/memory Deficits in an Alzheimer's Disease Rat Model. J Neural Transm (Vienna). 2012;119(11):1407-16. PubMed PMID: 22527777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer's disease rat model. AU - Han,Xiaojuan, AU - Ma,Yan, AU - Liu,Xiaohui, AU - Wang,Lu, AU - Qi,Shen, AU - Zhang,Qinghua, AU - Du,Yifeng, Y1 - 2012/04/17/ PY - 2011/11/01/received PY - 2012/03/29/accepted PY - 2012/4/25/entrez PY - 2012/4/25/pubmed PY - 2013/4/20/medline SP - 1407 EP - 16 JF - Journal of neural transmission (Vienna, Austria : 1996) JO - J Neural Transm (Vienna) VL - 119 IS - 11 N2 - Brain metabolic dysregulation is a hallmark pathological change in Alzheimer's disease (AD). Although detailed mechanisms are still not fully elucidated, recent studies suggest alterations of insulin-signaling transduction cascades underlie neuronal stresses in AD brains. In this study, we performed in vivo experiments to determine the impact of soluble Aβ oligomers on insulin-signaling transduction in rat hippocampi by utilizing lateral ventricular injection of amyloid beta (Aβ) oligomers on male Wistar rats (225 ± 25 g, 3-4 months old) as an AD rat model. The Aβ-infused rats manifested remarkably increased escape latency and significantly decreased proportions of time and pathway crossing the hidden platform as compared to the rats in the pseudo-injection group and the non-injection group in Morris water maze test implicating the damaging effect of soluble Aβ oligomers on rat learning and memory functions. Accordingly, our subsequent results demonstrated that the infusion of soluble Aβ oligomers significantly decreased the expressions of insulin receptor, insulin receptor substrate-I, B cell lymphoma/leukemia-2 and serine/threonine protein kinase B in rat hippocampal neurons, whereas the expression level of total cAMP response element-binding protein was not changed. This study suggests that soluble Aβ oligomers instigated insulin-signaling disturbances which are potentially associated with learning and memory deficits in the AD rat model. SN - 1435-1463 UR - https://www.unboundmedicine.com/medline/citation/22527777/Changes_in_insulin_signaling_transduction_pathway_underlie_learning/memory_deficits_in_an_Alzheimer's_disease_rat_model_ L2 - https://dx.doi.org/10.1007/s00702-012-0803-1 DB - PRIME DP - Unbound Medicine ER -