engleski

The potential protective role of dehydroepiandrosterone and its sulfate in the genetic and pharmacologically induced animal model of Alzheimer’s disease

Alzheimer's disease (AD) is the most prevalent form of dementia, accounting for 60-70% of all dementia cases. It is a progressive and incurable neurodegenerative disorder characterized by the amyloid beta (Aβ) peptide deposition in the amyloid plaques and accumulation of hyperphosphorylated tau protein in the neurofibrillary tangles. It affects neuronal functioning and connectivity, resulting in a progressive loss of brain functions, with the cortex and hippocampus being primarily affected. The current AD therapy is only effective in alleviating the symptoms, whereas ongoing research aims at discovering new disease-modifying treatment strategies. The neurosteroids dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) have been studied for their neuroprotective potential in AD. Although these steroid hormones are abundant in the human blood, they are also produced de novo in neurons and glial cells, where their concentration is 6-8 times higher in comparison to periphery. In our research, we have utilized both genetic and pharmacologically induced mouse model of AD. The triple-transgenic AD (3xTg-AD) mouse is one of the most appropriate animal models of AD, displaying all main histopathological and behavioral features of AD, including age-dependent development of amyloid plaques, neurofibrillary tangles and progressive cognitive decline. The 3xTg-AD mice and C57BL/6 control mice were chronically treated with DHEAS using subcutaneously intrascapulary implanted osmotic pumps. The pharmacologically induced AD model was established by intracerebroventriculary injecting the C57BL/6 mice with Aβ oligomers and chronically administered with DHEA via intraperitoneal injection. Various cognitive and behavioral tests were performed on both models and analyzed using Noldus EthoVision XT software. Upon completion of the treatments and behavioral testing, the mice were euthanized and their brains were harvested for further analysis. Our results suggest that DHEA(S) could potentially serve as a protective agent against cognitive decline and other symptomatic presentations in mouse models of AD. Nevertheless, further validation of these results is necessary and it is imperative to extend our findings to include human blood samples to investigate potential therapeutic strategies of these neurosteroids in the future.

Alzheimer´s disease ; DHEA ; DHEAS ; C57BL/6 ; 3xTg-AD

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