2025/07/31 by Josiane do Nascimento Silva, Bianca Andrade Rodrigues, Elisa Mitiko Kawamoto · 1 voice
Medicine · Neuroscience · #Apelin-related biomedical research #Cancer-related cognitive impairment studies #Neurogenesis and neuroplasticity mechanisms
paper · doi:10.1016/j.neumar.2025.100110
openalex publication_date 2025/07/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14
Adult hippocampal neurogenesis is a continuous process of generating new neurons from neural stem cells, occurring in specific brain regions such as the dentate gyrus of the hippocampus. This process is essential for neural plasticity, learning, and memory consolidation. Serotonin (5-hydroxytryptamine or 5-HT) plays a significant role in modulating this process by acting on different receptor subtypes expressed in the dentate gyrus. This narrative review explores the impacts of aging on 5-HT and hippocampal neurogenesis, highlighting the modulatory role of physical exercise in this regard. Bromodeoxyuridine as a neurogenesis marker reveals a decrease in the number of newborn neurons and impaired integration during brain aging. Evidence has shown that the activation of 5-HT receptors is associated with key stages of neurogenesis. During aging, functional and structural changes in the 5-HT system have been linked to a reduction in hippocampal neurogenesis, which may contribute to the cognitive decline observed in aging. In this context, physical exercise, especially aerobic exercise, emerges as a potent positive modulator of neurogenesis by directly influencing the activity of 5-HT neurons. Studies have demonstrated that various exercise protocols, when applied with appropriate intensity and duration, can increase cell proliferation in the dentate gyrus, even in aged individuals. Notably, aerobic exercise significantly improves the microenvironment of neurogenesis by enhancing the activity of 5-HTergic neurons, upregulating the density of 5-HT1A receptors and promoting the expression of brain-derived neurotrophic factors. Experimental studies have shown that exercise increases the proportion of bromodeoxyuridine-positive neurons and elevates serotonin transporter and 5-HT1A receptor expression. This suggests that exercise counteracts aging-related reduction in neurogenesis through multi-target mechanisms. However, most of the existing studies are based on rodent models, and clinical translational studies in humans still need to be in-depth explored. Therefore, regular physical exercise represents a promising strategy for mitigating the adverse effects of aging on hippocampal neurogenesis, reinforcing its relevance in maintaining brain function throughout life.