Melatonin promotes neurogenesis in dentate gyrus in the pinealectomized rat

Abstract

It was previously shown that pinealectomy causes delayed loss of pyramidal neurons in rat hippocampal layers CA1/3 and that this is reversed by melatonin supplementation. Here, we used immunohistologic detection of doublecortin, a protein expressed in newborn neurons, to determine if melatonin supplementation promotes neurogenesis after pinealectomy. It was found that melatonin supplementation significantly increased the number of doublecortin immunoreactive neurons in the dentate gyrus over the postsurgical intervals of 2, 4, 6, 8, 10 and 17 months. The increase was most evident at 6 months postsurgery and thereafter, and was apparent despite a severe decline in doublecortin-labeled cells over the 17 month postsurgical interval in all groups of rats. Doublecortin immunoreactive cells were not observed in the pyramidal layer itself. These results indicate that melatonin promotes neurogenesis in the dentate gyrus of pinealectomized rats. However, it is equivocal that these newborn neurons migrate to the pyramidal layer and account for the reappearance of neurons at this location in these rats. This study provides further evidence for a role of melatonin in promoting neurogenesis, adding another role to its already remarkably pleiotropic profile. The scope and significance of this newly discovered role remains to be determined.

Piromelatine ameliorates memory deficits associated with chronic mild stress-induced anhedonia in rats

“…Piromelatine had no effect in non-stressed rats, thereby behaving as a Bstate-dependent^drug. Our results are in accordance with data showing that melatonin acts as a positive endogenous regulator of neurogenesis during aging (Ramirez-Rodriguez et al 2012;Rennie et al 2009). …”

Melatonin maintains calcium-binding calretinin-positive neurons in the dentate gyrus during aging of Balb/C mice

“…In the same sense, adult hippocampal neurogenesis (Couillard-Despres et al, 2009;Jinno, 2011;Kuhn et al, 1996) and plasma melatonin levels are reduced during aging (Brusco et al, 2000;Liu et al, 1999;Waldhauser et al, 1993). However, supplementation with melatonin favors cell proliferation and survival, neuroblast population, and early post-mitotic neurons in the DG of rodents (Ramirez-Rodriguez et al, 2011, 2012Rennie et al, 2009). The fact that treatment with melatonin did not prevent the decline of CRpositive neurons may be a consequence of changes in the brain and systemic milieu that are modified during aging (Villeda et al, 2011).…”

“…Liu et al, 2013Ramirez-Rodriguez et al, 2009;Ramirez-Rodriguez et al, 2012;Rennie et al, 2009), it increased the number of CR-neurons in the DG of young female C57Bl6 mice (Ramirez-Rodriguez et al, 2009). However, to our knowledge, it is not known whether exogenous melatonin may affect the CR-neuronal population in the DG during aging in male Balb/C mice (Gomez-Corvera et al, 2009).…”

N-Acetylserotonin Increases Cell Proliferation and Differentiating Neuroblasts with Tertiary Dendrites through Upregulation of Brain-Derived Neurotrophic Factor in the Mouse Dentate Gyrus

“…For example, adult neurogenesis decreases with age [16,22], and slightly higher numbers of proliferating cells are found in the middle of the active period of the circadian rhythm [14]. Melatonin modulates reactive neurogenesis, and its supplementation after pinealectomy affects hippocampal neurogenesis [20,30]. In addition, melatonin levels decline during aging [26].…”