Abstract
Melatonin, the main product synthesized by the pineal gland, acts as a regulator of the generation of new neurons in the dentate gyrus (DG). Newborn neurons buffer the deleterious effects of stress and are involved in learning and memory processes. Furthermore, melatonin, through the regulation of the cytoskeleton, favors dendrite maturation of newborn neurons. Moreover, newborn neurons send their axons via the mossy fiber tract to Cornu Ammonis 3 (CA3) region to form synapses with pyramidal neurons. Thus, axons of newborn cells contribute to the mossy fiber projection and their plasticity correlates with better performance in several behavioral tasks. Thus, in this study, we analyzed the impact of exogenous melatonin (8 mg/kg) administered daily for one- or six-months on the structural plasticity of infrapyramidal- and suprapyramidal mossy fiber projection of granule cells in the DG in male Balb/C mice. We analyzed the mossy fiber projection through the staining of calbindin, that is a calcium-binding protein localized in dendrites and axons. We first found an increase in the number of calbindin-positive cells in the granular cell layer in the DG (11%, 33%) after treatment. Futhermore, we found an increase in the volume of suprapyramidal (>135%, 59%) and infrapyramidal (>128%, 36%) mossy fiber projection of granule neurons in the DG after treatment. We also found an increase in the volume of CA3 region (>146%, 33%) after treatment, suggesting that melatonin modulates the structural plasticity of the mossy fiber projection to establish functional synapses in the hippocampus. Together, the data suggest that, in addition to the previously reported effects of melatonin on the generation of new neurons and its antidepressant like effects, melatonin also modulates the structural plasticity of axons in granule cells in the DG.
Highlights
Melatonin is synthesized and released by the pineal gland [1,2]
We demonstrated that chronic administration of melatonin increases the number of calbindin-positive cells and affects the structural plasticity of both suprapyramidal and infrapyramidal mossy fiber projections identified with calbindin, the main calcium-buffering protein in mossy fibers [34], after one- or six-months of treatment in male Balb/C mice
We analyzed the effects of melatonin on the structural plasticity in the mossy fiber projection in the dentate gyrus after chronic treatment with melatonin in male Balb/C mice for one- or six-months
Summary
Melatonin is synthesized and released by the pineal gland [1,2]. The indole acts through membrane receptors [1,2]. Melatonin promotes cell survival, enhances dendrite maturation of new neurons, and the indole delays the decline of adult hippocampal neurogenesis [13,14,15,22,23,24,25]. In this regard, it has been suggested that some neuropsychiatric disorders occur with alterations of the hippocampal neurogenic process [26]. Reduced plasma melatonin levels are altered in several neuropsychiatric disorders including, but not limited to, Alzheimer’s disease, schizophrenia, obsessive-compulsive disorder This process occurs as we age [21,27,28]
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