Involvement of Testosterone Signaling in the Integrity of the Neurovascular Unit in the Male: Review of Evidence, Contradictions, and Hypothesis

Age-related central nervous system function decline and increased susceptibility of females compared to males with respect to prevalence of several neurodegenerative and neuropsychiatric diseases are both based on the principle that hormonal factors could be involved. These cerebral disorders are characterized by an alteration of blood-brain barrier (BBB) properties and chronic neuroinflammation, which lead to disease progression. Neuroinflammation, in turn, contributes to BBB dysfunction. The BBB and its environment, called the neurovascular unit (NVU), are crucial for cerebral homeostasis and neuronal function. Interestingly, sex steroids influence BBB properties and modulate neuroinflammatory responses. To date however, the majority of work reported has focused on the effects of estrogens on BBB function and neuroinflammation in female mammals. In contrast, the effects of testosterone signaling on the NVU in males are still poorly studied. The aim of this review was to summarize and discuss the literature, providing insights and contradictions to highlight hypothesis and the need for further investigations.