Ghrelin Regulates Hippocampal Neurogenesis in Adult Mice

Abstract

Rapid CommuniCationis principally released from Gr cells in the oxyntic mucosa of the stomach [5]. In addition to stimulating GH release via the hypothalamus and direct pituitary pathways and inducing a positive energy balance by stimulating food intake while decreasing fat use through GH-independent mechanisms, ghrelin has been suggested to have numerous peripheral actions including direct effects on exocrine and endocrine pancreatic functions, carbohydrate metabolism, the cardiovascular system, gastric secretion, stomach motility, and sleep [6]. It has been reported that maternal ghrelin plays an important role in rat fetal development during pregnancy [7]. Ghrelin is also involved in neurogenesis of the rat fetal spinal cord [8]. In addition, in the nucleus of the solitary tract (NTS) [9] and the dorsal motor nucleus of vagus (DMNV) [10] in adult rats with cervical vagotomy, ghrelin promotes neural proliferation in vivo and in vitro. Moreover, very recently it has been reported that ghrelin increases cellular proliferation of adult rat hippocampal progenitor cells in vitro [11]. However, there is no report to date about the effect of ghrelin on neurogenesis in the adult mammalian SGZ of the DG in vivo. In the present study, we wanted to study the impact of systemically administered ghrelin. Therefore, the aim of this study was to investigate the proliferation and differentiation of Medicine, Seoul, Korea abstract. The aim of our study was to investigate the effect of the peripheral administration of ghrelin, a peptide hormone secreted from the stomach, on cellular proliferation and differentiation of progenitor cells in the adult hippocampus. Double immunohistochemical staining revealed that ki-67-positive hippocampal progenitor cells expressed ghrelin receptors. In mice treated with ghrelin (80 µg/kg, i.p.) for 8 days, bromodeoxyuridine incorporation and doublecortin-positive neuroblasts were significantly increased in the dentate subgranular zone. We also found that the numbers of bromodeoxyuridine-and doublecortin-immunoreactive cells were significantly reduced after anti-ghrelin antibody (10 µg/kg, i.p.) treatment for 8 days. Therefore, our results indicate that ghrelin induces proliferation and differentiation of adult hippocampal progenitors, suggesting an involvement of ghrelin in hippocampal neurogenesis.

Multiple signaling pathways mediate ghrelin-induced proliferation of hippocampal neural stem cells

“…Initially, ghrelin was known to increase neurogenesis in the rat fetal spinal cord (Sato et al 2006) and the nucleus of the solitary tract (Zhang et al 2005) and the dorsal motor nucleus of vagus in adult rats. We previously reported that systemic administration of ghrelin induces hippocampal neurogenesis in adult mice (Moon et al 2009b). Moreover, in our recent study (Li et al 2013), we found that ghrelin knockout mice showed lower numbers of progenitor cells in the DG of the hippocampus, while ghrelin treatment restored the numbers of progenitor cells to those of the wild-type controls.…”

“…In the current study, we clearly showed that the ghrelin receptor was expressed in cultured adult rat hippocampal NSCs at the protein levels, which were assessed by two independent methods (western blot analysis and immunocytochemistry). GHS-R1a was also found in hippocampal progenitor cells in adult mice (Moon et al 2009b). The effect of ghrelin on the proliferation of adult rat hippocampal NSCs appears to be mediated through the activation of GHS-R1a because the treatment of the receptor-specific antagonist D-Lys-3-GHRP-6 completely blocked the proliferative effect of ghrelin.…”

Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice

“…Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.Key words: Ghrelin, Adult neurogenesis, Hippocampus, Dietary restriction lar zone (SGZ) [6]. Additionally, in our recent report [7], we found that mice with targeted disruption of the ghrelin gene showed a decreased number of progenitor cells in the dentate gyrus (DG) of the hippocampus, while ghrelin replacement restored progenitor cell numbers to those of wild-type (WT) controls.…”

“…Key words: Ghrelin, Adult neurogenesis, Hippocampus, Dietary restriction lar zone (SGZ) [6]. Additionally, in our recent report [7], we found that mice with targeted disruption of the ghrelin gene showed a decreased number of progenitor cells in the dentate gyrus (DG) of the hippocampus, while ghrelin replacement restored progenitor cell numbers to those of wild-type (WT) controls.…”

Ghrelin directly stimulates adult hippocampal neurogenesis: implications for learning and memory

“…Initially, ghrelin was shown to increase neurogenesis in the dorsal motor nucleus of vagus [4], the nucleus of the solitary tract [5] and the rat fetal spinal cord [6] in adult rats. We recently have reported that systemic administration of ghrelin stimulates proliferation of newly generating cells in the hippocampus of adult mice [7]. Moreover, immunoneutralization of ghrelin by using anti-ghrelin antiserum in adult mice reduces proliferation of hippocampal progenitor cells in the SGZ [7].…”