Melatonin increases proliferation of cultured neural stem cells obtained from adult mouse subventricular zone

Abstract

Melatonin, a circadian rhythm-promoting molecule secreted mainly by the pineal gland, has a variety of biological functions and neuroprotective effects including control of sleep-wake cycle, seasonal reproduction, and body temperature as well as preventing neuronal cell death induced by neurotoxic substances. Melatonin also modulates neural stem cell (NSC) function including proliferation and differentiation in embryonic brain tissue. However, the involvement of melatonin in adult neurogenesis is still not clear. Here, we report that precursor cells from adult mouse subventricular zone (SVZ) of the lateral ventricle, the main neurogenic area of the adult brain, express melatonin receptors. In addition, precursor cells derived from this area treated with melatonin exhibited increased proliferative activity. However, when cells were treated with luzindole, a competitive inhibitor of melatonin receptors, or pertussis toxin, an uncoupler of Gi from adenylate cyclase, melatonin-induced proliferation was reduced. Under these conditions, melatonin induced the differentiation of precursor cells to neuronal cells without an upregulation of the number of glia cells. Because stem cell replacement is thought to play an important therapeutic role in neurodegenerative diseases, melatonin might be beneficial for stimulating endogenous neural stem cells.

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

“…Melatonin also stimulates the proliferation and differentiation of neural stem cells in the SVZ (86). During aging, the capacity for neurogenesis mostly declines, although some evidence shows a constant capacity (87).…”

“…The melatonin receptors MT 1 (102,86) and MT 2 (103) are expressed in neural stem cells. High concentrations of melatonin in an exposure-timing-dependent manner (104) and at physiologic concentration, particularly through MT 1 receptors in the SVZ, have a modulatory effect on neural stem cell proliferation and differentiation (86).…”

“…High concentrations of melatonin in an exposure-timing-dependent manner (104) and at physiologic concentration, particularly through MT 1 receptors in the SVZ, have a modulatory effect on neural stem cell proliferation and differentiation (86). Recent studies have identified functions in neurogenesis for MT 1 and MT 2 agonists, including agomelatine (105,106), buspirone in combination with melatonin in major depressive disorder (107), and Nacetylserotonin, an intermediate of melatonin synthesis (108).…”

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

“…CVOs bridge endocrine and autonomic phenomena (Uschakov et al 2009), particularly the homeostatic adjustment of fluid composition, volume, and osmolality (Henry, Grob, and Mouginot 2009). CVOs are sites of action or release of fluid-regulating peptidergic neurotransmitters, cytokines, and hormones (Feher et al 2010;Sotthibundhu, Phansuwan-Pujito, and Govitrapong 2010). Anatomically, CP is not a CVO because the preponderance of choroidal tissue does not reside in the ventricular wall.…”

Age-Related Changes in the Melatonin and Thymulin Biorhythms as Risk Factors for Human Neurodegenerative Diseases

“…Thus, in adult brain there occurs circadian rhythmicity in the proliferation of neural stem cells (NSCs) [12] and olygodendrocyte functioning [13]. Melatonin enhances proliferation and differentiation of NSCs in the subventricular zone of the hypothalamus via stimulation of expression of brain growth factors [14]. Data about influence of sex and glucocorticoid hormones on the brain neurogenesis were reported [15,16].…”