Juan Luis Blázquez

Antidepressant-related sexual dysfunction is a frequent adverse event caused by serotonergic activation that intensely affects quality of life and adherence in depressed patients. The dopamine system has multiple effects promoting sexual behavior, but no studies have been carried out to confirm dopaminergic changes involved in animal models after antidepressant use. Methods: The sexual behavior-related dopaminergic system in the rat was studied by comparing two different antidepressants and placebo for 28 days. The antidepressants used were paroxetine (a serotonergic antidepressant that causes highly frequent sexual dysfunction in humans) and agomelatine (a non-serotonergic antidepressant without associated sexual dysfunction). The tyrosine hydroxylase immunoreactivity (THI) in the substantia nigra pars compacta, the ventral tegmental area, the zona incerta, and the hypothalamic arcuate nucleus, as well as the dopaminergic projections to the striatum, hippocampus, cortex, and median eminence were analyzed. Results: The THI decreased significantly in the substantia nigra and ventral tegmental area after treatment with paroxetine, and the labeling was reduced drastically in the zona incerta and mediobasal hypothalamus. The immunoreactive axons in the target regions (striatum, cortex, hippocampus, and median eminence) almost disappeared only in the paroxetine-treated rats. Conversely, after treatment with agomelatine, a moderate reduction in immunoreactivity in the substantia nigra was found without appreciable modifications in the ventral tegmental area, zona incerta, and mediobasal hypothalamus. Nevertheless, no sexual or copulatory behavior was observed in any of the experimental or control groups. Conclusion: Paroxetine but not agomelatine was associated with important decreased activity in dopaminergic areas such as the substantia nigra and ventral tegmental areas that could be associated with sexual performance impairment in humans after antidepressant treatment.

Despite decades of research, no compelling non-surgical therapies have been developed for foetal hydrocephalus. So far, most efforts have pointed to repairing disturbances in the cerebrospinal fluid (CSF) flow and to avoid further brain damage. There are no reports trying to prevent or diminish abnormalities in brain development which are inseparably associated with hydrocephalus. A key problem in the treatment of hydrocephalus is the blood–brain barrier that restricts the access to the brain for therapeutic compounds or systemically grafted cells. Recent investigations have started to open an avenue for the development of a cell therapy for foetal-onset hydrocephalus. Potential cells to be used for brain grafting include: (1) pluripotential neural stem cells; (2) mesenchymal stem cells; (3) genetically-engineered stem cells; (4) choroid plexus cells and (5) subcommissural organ cells. Expected outcomes are a proper microenvironment for the embryonic neurogenic niche and, consequent normal brain development.