Boosting Neurogenesis in the Adult Hippocampus Using Antidepressants and Mesenchymal Stem Cells

Abstract

The hippocampus is one of the few privileged regions (neural stem cell niche) of the brain, where neural stem cells differentiate into new neurons throughout adulthood. However, dysregulation of hippocampal neurogenesis with aging, injury, depression and neurodegenerative disease leads to debilitating cognitive impacts. These debilitating symptoms deteriorate the quality of life in the afflicted individuals. Impaired hippocampal neurogenesis is especially difficult to rescue with increasing age and neurodegeneration. However, the potential to boost endogenous Wnt signaling by influencing pathway modulators such as receptors, agonists, and antagonists through drug and cell therapy-based interventions offers hope. Restoration and augmentation of hampered Wnt signaling to facilitate increased hippocampal neurogenesis would serve as an endogenous repair mechanism and contribute to hippocampal structural and functional plasticity. This review focuses on the possible interaction between neurogenesis and Wnt signaling under the control of antidepressants and mesenchymal stem cells (MSCs) to overcome debilitating symptoms caused by age, diseases, or environmental factors such as stress. It will also address some current limitations hindering the direct extrapolation of research from animal models to human application, and the technical challenges associated with the MSCs and their cellular products as potential therapeutic solutions.

Increased volume of the left hippocampal dentate gyrus after 4 weeks of bright light exposure in patients with mood disorders: a randomized controlled study

“…Mood stabilizers such as lithium, antidepressants (e.g. selective serotonin reuptake inhibitors [SSRIs]), and electroconvulsive therapy, increase adult hippocampal neurogenesis [11,12,13,14,15,16]. In our study, signi cant volumetric changes were observed in the hippocampal left DG-head and left DG-total in the BL group but not in the DL group.…”

Adult hippocampal neurogenesis: pharmacological mechanisms of antidepressant active ingredients in traditional Chinese medicine

“…Dysfunction of the hippocampus due to aging, injury, depression, or neurodegenerative diseases can lead to cognitive decline, significantly affecting the quality of life for individuals. Antidepressant treatments hold promise in directly or indirectly promoting AHN and alleviating depressive symptoms ( Kot et al, 2022 ). SSRIs, commonly prescribed antidepressants, exert their effects by selectively blocking the reuptake of 5-HT, thereby prolonging and enhancing its activity ( Perez-Caballero et al, 2014 ; Bi et al, 2022 ).…”