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In Vitro and In Vivo Studies of Prolonged DHEA(S) Treatment

Dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) are neurosteroids involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, therefore demonstrating the potential for treatment of different neuropsychiatric and cognitive disorders. Although the underlying molecular mechanisms are not clear, the observed beneficial actions of DHEA(S) such as pro-immune, anti-dementia, anti-aging and many other effects probably require a rather long- term therapeutic strategy. However, the potential development of tolerance and dependence as well as possible increased susceptibility to seizures following prolonged treatment may limit DHEA(S) clinical use. Given the chronic nature of many conditions for which DHEA(S) could be prescribed, in addition to the current literature data, we also review recent findings of our in vitro and in vivo studies, investigating the potential of prolonged DHEA(S) treatment to influence the neuronal excitability and to induce adaptive changes of GABAA receptors usually associated with the development of tolerance and dependence. Fortunately, the results of in vitro and in vivo studies investigating the effects of prolonged exposure to DHEA(S) suggest that this neurosteroid might be safe for various potential therapeutic applications. Our findings also point to the discrete interaction of DHEA(S) with male and female hormonal status, which may result in the observed gender-related differences in the various effects of DHEA(S) on health and morbidity. Since the molecular mechanisms of DHEA(S) are still not clear, further studies should elucidate the role of GABAergic as well as other neurotransmitter systems in these complex actions of DHEA(S).

neurosteroids, dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), neuronal excitability, development of tolerance and dependence, mice, cell culture

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