Therapeutic potential of neurosteroids and neurotrophins in dementia

Dementia is a syndrome of progressive cognitive decline that usually affects older people. It will become one of the leading global problems in the future due to accelerated aging of the population and increase of life expectancy. Alzheimer´s disease (AD) is the most common progressive and incurable neurodegenerative disease. Neuroimaging techniques have shown a decrease in brain volume and weight in AD patients, as well as dilation of lateral brain chambers, while post-mortem studies have found extracellular accumulations of amyloid beta (Aβ) in senile plaques and intracellular neurofibrillary tangles as a result of accumulating hyperphosphorylated tau protein. Current available therapy is based on symptomatic treatment or alleviation of disease symptoms and numerous studies of new effective drugs have failed. Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), the most abundant steroids in human blood whose concentrations decrease significantly with aging, are involved in brain functions such as neural plasticity, learning, memory and behavior and have anti-inflammatory, antioxidant and anti-glucocorticoid effects. Brainderived neurotrophic factor (BDNF) is one of trophic factors that is involved in various aspects of neuronal development and differentiation, as well as plasticity and repair mechanisms. BDNF promotes the survival and differentiation of neurons that are damaged in AD. The purpose of this study is to investigate the neuroprotective potential and mechanisms of action of DHEA(S) and BDNF in dementia, through a combination of cellular, animal and human experiments. Currently, we are conducting in vitro experiments in which we study the protective effects of DHEA(S) and BDNF on isolated primary neurons from C57BL/6 mouse strain, treated with toxic Aβ-oligomers.