GalR2/3 mediates proliferative and trophic effects of galanin on postnatal hippocampal precursors

Abstract

1These authors contributed equally to this work.Abbreviations used: BrdU, bromodeoxyuridine; DAPI, 4¢,6-diamidino-2-phenylindole; DG, dentate gyrus; DIV, days in vitro; GalR1, galanin receptor-1; GFAP, glial fibrillary acidic protein; KO, knock-out; LI, labelling index; NB, neurobasal; NPY, neuropeptide Y; NSPCs, neural stem progenitor cells; PBS, phosphate-buffered saline; PI, propidium iodide; SGZ, subgranular zone. AbstractUnderstanding how neural activity is functionally linked to the stem cell niche, is assuming ever increasing importance as hippocampal neurogenesis is shown to be important for modulating the behavioural responses to stress and for certain forms of learning and memory. Neuropeptides such as neuropeptide Y and vasoactive intestinal peptide have emerged as important mediators for signalling local interneuron activity to subgranular zone precursors, however, little is known regarding the effects of neuropeptides that are extrinsic modulators of hippocampal information processing. Here, we show that the galanin GalR2/3 agonist Gal2-11 is both trophic and proliferative for postnatal subgranular precursors and proliferating neuroblasts at 10 nM and is purely trophic at doses as low as 100 pM. We found no effect mediated via GalR1. As galanin is co-released from noradrenergic and serotonergic projection neurons to the dentate gyrus, these findings support a direct effect of galanin on hippocampal neurogenesis, which may partly mediate its antidepressant effect via GalR2/3 receptors.

Effects of Exogenous Galanin on Neuropathic Pain State and Change of Galanin and Its Receptors in DRG and SDH after Sciatic Nerve-Pinch Injury in Rat

“…In contrast to GalR1, which only couple to Gi protein, GalR2 can also activate Gq/11 protein leading to more complex functions [45]. Many studies pay close attention to neuroprotective and neuronal trophic effect of Gal conducted by GalR2 [46], [47]. In the present study, the GalR2 in DRG and SDH was upregulated, which makes the increasing Gal acts as neurotrophin more effective.…”

Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition

“…By combining the DNA methylation pattern with gene expression analysis, 39 genes were found to be both hypermethylated and down-regulated in NPCs isolated from the DG of adult Tet1 KO Nestin -GFP mice and FACS-sorted for the Nestin -GFP + cells (Figure 4C and Table S1). Gene-specific qPCR and bisulfite sequencing confirmed the altered expression and methylation of several genes involved in neural progenitor proliferation, neuroprotection and mitochondria function, including Galanin, Ng2, Ngb, Kctd14 and Atp5h (Abbosh et al, 2011; Burmester et al, 2000; Calingasan et al, 2008; Kucharova and Stallcup, 2010) (Figures 4D and 4E). Considering that traditional bisulfite sequencing cannot distinguish 5mC from 5hmC (Huang et al, 2010), we examined hydroxymethylation at the promoter of these genes by Tet-assisted bisulfite sequencing (TAB- Seq) (Yu et al, 2012).…”

“…We showed a great enrichment of genes with aberrant promoter hypermethylation and decreased expression in Tet1 deficient NPCs. Among these genes, Galanin and Ng2 are best known for the regulation of neurogenesis (Abbosh et al, 2011; Deng et al, 2010; Kucharova and Stallcup, 2010); Ngb acts as hypoxia-inducible neuroprotective factor in hypoxic ischemic injury (Burmester et al, 2000; Moens and Dewilde, 2000; Sun et al, 2001); Kctd14 and Atp5h are associated with mitochondria function, which can affect adult neurogenesis indirectly (Calingasan et al, 2008). Thus, Tet1 deficiency leads to transcriptional repression of neurogenesis-related genes through promoter hypermethylation possibly due to impaired demethylation.…”

Galanin mediates features of neural and behavioral stress resilience afforded by exercise

“…Microarray profiling also shows that galanin expression distinguishes resilient and susceptible phenotypes (Krishnan et al, 2007). Although widely recognized for its neuromodulatory actions, galanin also has potent neurotrophic activity (Abbosh et al, 2011; Cordero-Llana et al, 2014; Hobson et al, 2008) and may alter the plasticity of neurons in regions that mediate resilience. Galanin may modulate catecholamine transmission in stress-responsive neural pathways (Holmes and Picciotto, 2006), either locally within the LC or in distal targets like the VTA or mPFC.…”