Il sistema serotoninergico tronco encefalico e la proliferazione cellulare nella zona sottoventricolare di ratti maschi adulti sono regolati dagli ormoni gonadici.

Adult neurogenesis is mostly limited to two major regions of the rodent brain: the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ)-olfactory bulb (OB) system. Gonadal hormones like estradiol (E2) and testosterone (T), play an important sexually dimorphic role as mediators of cell proliferation in the lateral wall of adult male rat SVZ. As previously reported, in male castrated rats, T and E2 administrations induce a strong increase of SVZ proliferation in comparison with castrated animals, but the mechanism is still unclear. There are two hypothesis: the first is a direct effect of E2 on the proliferating cells of the SVZ through its receptors (but up to now there is no evidence of the presence of these receptors in the SVZ), while the second is a possible trans-synaptic effect mediated by groups of estradiol-sensitive neurons located in others cerebral areas. A possible candidate for this is the serotonin (5-HT) system located within the dorsal raphe (DRN) projecting to the SVZ. In addition to its role as neurohormone and neurotransmitter, serotonin is considered a developmental regulatory signal, implicated in several aspects of neuronal differentiation like axonal growth and dendritic spine formation, and it is known to influence learning, memory and synaptic plasticity by maintaining the synaptic connections in the cortex and hippocampus. Moreover, a large number of estrogen receptors (ER alpha, ER beta and GPR30) is present in the DRN suggesting a possible modulation by gonadal hormones of this serotoninergic nucleus. We have, therefore, investigated the changes of 5-HT innervation in SVZ in adult male rat castrated, treated with E2, T, vehicle, or sham-operated. We performed a quantitative analysis of both 5-HT fibers in three different regions of SVZ (dorsal area, lateral and medial wall of the lateral ventricle) and of 5-HT positive neurons in DRN. Our results reveal that castration induces, in the lateral wall of SVZ, a significant decrease of 5-HT fibers in comparison to sham-operated animals. In DNR, the quantitative analysis show that in castrated animals there is also a significant decrease of 5-HT positive structures in comparison with sham-operated group. Moreover, data show that the treatment with E2 and T produce a strong increase of the 5-HT positive neurons and fibers in comparison with castrated animals. In conclusion, these results demonstrate that gonadal hormones modulate in the same way the serotoninergic system of the DRN, the fibers innervating the SVZ, and the cell proliferation in adult male rats, and suggest a serotonin effect on the regulation of adult neurogenesis at the SVZ level. Future studies should elucidate the molecular component of this mechanism.