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Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer’s disease rat model

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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.

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Acknowledgments

This study was supported by the Natural Science Foundation of Shandong Province (Y2008C116). We thank Dr. Edward C. Mignot for linguistic advice and Professor Shuli Sheng and Heng Du for revisal advice.

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Authors and Affiliations

  1. Department of Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jingwu Weiqi Road, Jinan, 250021, People’s Republic of China

    Xiaojuan Han, Xiaohui Liu, Lu Wang, Shen Qi, Qinghua Zhang & Yifeng Du

  2. Department of Neurology, No. 1 Central Hospital of Bao Ding City, Baoding, Hebei, People’s Republic of China

    Yan Ma

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  1. Xiaojuan Han
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  2. Yan Ma
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  3. Xiaohui Liu
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  7. Yifeng Du
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Correspondence to Yifeng Du.

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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 119, 1407–1416 (2012). https://doi.org/10.1007/s00702-012-0803-1

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  • DOI: https://doi.org/10.1007/s00702-012-0803-1

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