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褪黑素通过调节雄性 Balb/C 小鼠背侧和腹侧齿状回树突的成熟和复杂性发挥其抗抑郁样作用。

Melatonin Modulates Dendrite Maturation and Complexity in the Dorsal- and Ventral- Dentate Gyrus Concomitantly with Its Antidepressant-Like Effect in Male Balb/C Mice.

机构信息

Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico.

Laboratory of Neuropsychopharmacology, Division of Neurosciences, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calzada Mexico-Xochimilco No. 101, Mexico City C.P. 14370, Mexico.

出版信息

Int J Mol Sci. 2020 Mar 3;21(5):1724. doi: 10.3390/ijms21051724.

Abstract

Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including antidepressant drugs, environmental modifications and internal factors act pro-neurogenic with consequences in the dorsal and ventral DG. Melatonin, the main product synthesized by the pineal gland, induces antidepressant-like effects and modulates several events of the neurogenic process. However, the information related to the capability of melatonin to modulate dendrite maturation and complexity in the dorsal and ventral regions of the DG and their correlation with its antidepressant-like effect is absent. Thus, in this study, we analyzed the impact of melatonin (0, 0.5, 1, 2.5, 5 or 10 mg/kg) administered daily for fourteen days on the number, dendrite complexity and distribution of doublecortin (DCX)-cells in the dorsal-ventral regions of the DG in male Balb/C mice. Doublecortin is a microtubule-associated protein that is expressed during the course of dendritic maturation of newborn neurons. Also, we analyzed the impact of melatonin on despair-like behavior in the forced swim test. We first found a significant increase in the number and higher dendrite complexity, mainly with the doses of 2.5, 5 and 10 mg/kg of melatonin (81%, 122%, 78%). These cells showed more complex dendritic trees in the ventral- and the dorsal- DG. Concomitantly, the doses of 5 and 10 mg/kg of melatonin decreased depressant-like behavior (76%, 82%). Finally, the data corroborate the antidepressant-like effect of melatonin and the increasing number of doublecortin-associated cells. Besides, the data indicate that melatonin favors the number and dendrite complexity of DCX-cells in the dorsal- and ventral- region of the DG, which may explain part of the antidepressant-like effect of melatonin.

摘要

成人神经发生发生在海马的齿状回(DG)中。新神经元有助于抵消应激的影响,包括抗抑郁药、环境改变和内部因素在内的几种干预措施具有促神经发生作用,其后果表现在背侧和腹侧 DG。褪黑素是松果腺合成的主要产物,它诱导抗抑郁样作用,并调节神经发生过程中的几个事件。然而,关于褪黑素调节背侧和腹侧 DG 中树突成熟和复杂性及其与抗抑郁样作用的相关性的信息尚不清楚。因此,在这项研究中,我们分析了褪黑素(0、0.5、1、2.5、5 或 10 mg/kg)连续 14 天给药对雄性 Balb/C 小鼠 DG 背腹区 DCX 细胞数量、树突复杂性和分布的影响。双皮质蛋白(DCX)是一种微管相关蛋白,在新生神经元树突成熟过程中表达。此外,我们还分析了褪黑素对强迫游泳试验中绝望样行为的影响。我们首先发现,褪黑素的剂量为 2.5、5 和 10 mg/kg 时,细胞数量显著增加,树突复杂性更高(81%、122%和 78%)。这些细胞在 DG 的腹侧和背侧显示出更复杂的树突。同时,5 和 10 mg/kg 的褪黑素剂量降低了抑郁样行为(76%、82%)。最后,数据证实了褪黑素的抗抑郁样作用和与双皮质蛋白相关细胞数量的增加。此外,数据表明,褪黑素有利于 DG 的背侧和腹侧区域中 DCX 细胞的数量和树突复杂性,这可能解释了褪黑素抗抑郁样作用的部分原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9e3/7084558/6b4bb51488fa/ijms-21-01724-g001.jpg

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