engleski

Amyloid precursor protein, neuroplastin, insulin and leptin receptors – a role in gender differences in memory impairment upon aging and stress

Introduction: Many proteins are involved in molecular mechanisms of neurodegeneration. In this study we analyzed proteins that are highly associated with lipid rafts (LR) - amyloid precursor protein (APP), insulin receptor (IR), leptin receptor (ObR) and neuroplastin (Np) - in hippocampus and cerebella of chronically stressed male and female rats. LR create molecular environment of receptors that is critical for downstream signaling. Aim of the study was to determine receptor association with LR as possible pathophysiological substrate behind gender differences in memory impairment upon aging and stress. Methods: Male and female Sprague Dawley rats were divided in young (6, 5 months old) and old (14, 5 months old) group. Chronic stress protocol was performed for 10 weeks. LR were isolated from hippocampi and cerebella. APP, IR, ObR and Np were screened in membrane proteins, LR and non LR fractions (nLR) by Western blotting. Memory impairment was tested by passive avoidance test. All data was analyzed by the Statistica software. Results: APP was detected mostly in nLR membrane fractions and IR, ObR and Np were detected in both LR and nLR fractions with some distinctions. All analyzed proteins showed expressional changes upon chronic stress. Behavioral testing demonstrated memory impairment in old female chronic stress group as compared to young female chronic stress group (U=0, N1=N2=9, p=0.00004) while male animals had no statistically significant changes in memory compared to other animal groups. Discussion and Conclusion: Chronic stress, not aging itself, is associated with memory impairment that is specifically observed in old female animals. Changes in analyzed proteins upon stress implicate its connection with HPA axis and specific changes of IR and ObR upon chronic stress confirm a strong connection of cell metabolism with neurodegeneration. Acknowledgments: This study has been funded by Croatian Science Foundation (IP-09-2014-2324) and Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program and the RECOOP HST Association. Part of this study was performed at the Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, under the supervision of prof. Robert Gaspar. Ethical Committee Approval: Experiments were carried out at Animal Facility of Faculty of Medicine Osijek and was approved under class number 602-04/14-08/06 and registration number 2158-61-07-14-118 and Animal Facility of Faculty of Pharmacy, Szeged, approval number: CSI/01/3796- 7/2015.

stress ; aging ; neurodegeneration ; lipid rafts

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