Androgen receptor is expressed in murine choroid plexuses and downregulated by 5?-dihydrotestosterone in male and female mice

• Autor(a) principal: Alves, Celso Henrique Freitas
• Data de Publicação: 2008
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/1057
• topic: Doença de Alzheimer; Receptor de androgénios; Plexos coróideu; Neuroesteróides

Alzheimer’s disease (AD) is one of the major health problems in the economically developed countries. It is characterised by the progressive deterioration of memory and higher cortical functions, that ultimately result in total degradation of intellectual and mental activities. The key neuropathological characteristics of AD are: senile plaques (SP), which are associated with β-amyloid peptide (Aβ), neurofibrillary tangles (NFT), and the loss of neurons. Several studies showed that morphological and functional alterations in the choroid plexuses (CPs) are related to AD. The CPs of the brain form a unique interface between the peripheral blood and the cerebrospinal fluid (CSF). Peptides involved in neuroprotection, like nerve growth factor (NGF), transforming growth factor β (TGF-β), brain derived nerve factor (BDNF), transthyretin (TTR), and glial cell line-derived neurotrophic factor (GDNF), are secreted by CPs, and are regulated by androgens in other tissues, but the mechanisms underlying the regulation of these peptides in CPs remain unknown. Moreover, there are several experimental evidences showing that androgens enhance cognition and act as potential protective factors against degenerative diseases. It has been shown that testosterone exerts neuroprotective actions against oxidative stress, apoptosis, and against the toxicity of Aβ, all via androgen receptor (AR). AR has been identified in several regions of the central nervous system (CNS): hypothalamus, amygdala, hippocampus and the cortex, but not in the CPs. The presence of AR in CPs has never been investigated; neither the CPs have been considered a potential androgen responsive tissue. In order to fulfil this gap, we investigated and characterised AR distribution and expression in male and female rat CPs, and analysed its response to 5α-dihydrotestosterone (DHT), in castrated male and female mice, subjected to DHT replacement. We show that AR is expressed in rat CPs epithelial cells, and seems to be more abundant in female CPs than in males’. Moreover, we demonstrate that AR is down-regulated by DHT in mice CPs, an effect more prominent in females than in males.