Exploring the influence of adipokines on neuronal function in Alzheimer’s disease

Tomar, NS 2021, Exploring the influence of adipokines on neuronal function in Alzheimer’s disease , PhD thesis, University of Salford.

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Abstract

Alzheimer’s disease (AD) is one of the major causes of dementia. Alzheimer’s disease is an irreversible, slow neurodegenerative disease leading to memory and language impairment and amyloid-β plaques and intraneuronal neurofibrillary tangles are the characteristic pathology of AD. Studies have shown that obesity is major risk factor in Alzheimer’s disease. While obesity related modulation has been suggested to influence AD pathogenesis, the molecular mechanisms involved are still unclear. Recent research has shown that adipocytes can actively secrete adipokines and these adipokines may possess the ability to influence AD pathology, but it remains poorly understood how adipokines impact neural functioning. The current study was focused on the potential neuroprotective effect of adipokines on the neurons during hydrogen peroxide (H2O2) induced oxidative stress and cell death. In this study, human neuroblastoma SHSY5Y cells were differentiated using retinoic acid to demonstrate neuronal-like characteristics which was confirmed by immunocytochemistry (ICC). The pre-adipocytes 3T3-L1 cells, were chemically differentiated to exhibit adipocyte-like characteristics (determined by Oil-Red-O staining). To understand the potential rescue effect of conditioned media from adipocyte-like cells on neuronal-like cells, and commercially available adipokines (chemerin, leptin and resistin) on neuronal-like cells and effect of chemerin on human skin fibroblast cells derived from AD and non-AD donors, MTT assay was performed in the presence and absence of H2O2 induced oxidative stress. Conclusively, the conditioned media and commercial adipokines showed protective effects on the neuronal-like cells (*p<0.05, **p<0.01, ***p<0.001) in comparison to the non-neuronal cells and chemerin showed no protective effect in AD patient derived cells under H2O2 induced oxidative stress in comparison to the non-AD donors derived fibroblast cells. Neuroprotection was not observed in the obesity mimicked induced oxidative stress condition. Our findings suggested that the adipokines might play vital role in neuronal-like cellular metabolic protection against oxidative stress and warrants further investigation of the role of adipokines dysregulation in Alzheimer’s disease.

Item Type: Thesis (PhD)
Contributors: Withers, SB (Supervisor) and Lace-Perrin, GL (Supervisor)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Depositing User: Neha SantoshKumar Tomar
Date Deposited: 05 Oct 2021 14:31
Last Modified: 05 Oct 2021 14:31
URI: http://usir.salford.ac.uk/id/eprint/61826

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