The galanin receptor 2/3 agonist Gal2‐11 protects the SN56 cells against β‐amyloid_25–35 toxicity

Abstract

The neuropeptide galanin is a modulator of cholinergic function and may play a role in A beta peptide-induced degeneration of cholinergic forebrain neurons. We have studied the effect of galanin and its galanin receptor subtype 2/3 agonist Gal2-11on toxicity induced by freshly-prepared beta-amyloid(25-35) in the cholinergic cell line SN56. Both nuclear fragmentation and caspase-3 expression were analysed. beta-amyloid(25-35)-exposure induced a significant increase in caspase-3 mRNA expression after 30, 60, 90 or 150 min of beta-amyloid(25-35) exposure. These effects were abolished in the presence of Gal2-11 (10 nM). Similarly, beta-amyloid(25-35)-induced nuclear fragmentation was prevented by the galanin agonist at all time points studied. These findings indicate that the galanin 2/3 agonist Gal2-11 protects SN56 cholinergic cells from beta-amyloid(25-35)-induced cell death and that this action is mediated by an early reduction of caspase-3 expression.

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…Cheng and Yu (2010) demonstrated that galanin inhibited the neurotoxicity and associated gene expression induced by amyloid-b (25-35) (Ab (25-35)) or Ab (1-42) in rat primary cultured hippocampal neurons, with activity associated with GAL 2/3 activation using galanin (2-11) 144 (Cheng and Yu, 2010). Similar results were also reported independently (Elliott-Hunt et al, 2011) and using cultured human primary neurons (Cui et al, 2010) and a mouse cholinergic cell line, SN56 (Pirondi et al, 2010), with GAL 2/3 -mediated effects on cell death-related gene expression (e.g., caspase-3) implicated.…”

Endogenous Galanin Protects Mouse Hippocampal Neurons Against Amyloid Toxicity in vitro via Activation of Galanin Receptor-2

“…Treatment of cultured human embryonic cortical neurons with galanin significantly inhibited Aβ-induced cell death [39]. Similarly, galanin and Gal2-11 both significantly reduced Aβ toxicity in primary rat hippocampal [37] or cholinergic [38] neuronal cultures, and in cholinergic septal neuron 56 cells (a hybrid of mouse septal neurons and N18TG2 neuroblastoma cells) [40]. …”

“…Most recently, several studies have demonstrated that the addition of exogenous galanin or Gal2-11 is neuroprotective against Aβ toxicity in primary rat hippocampal [37] or cholinergic [38] cultures, human fetal brain cultures [39], and in the SN56 cholinergic cell line [40], and maintains or increases the expression of cell survival genes in the AD basal forebrain [41]. Here we show by modulation of endogenous levels of galanin or GAL 2 in transgenic mice, that the neuropeptide has a significant neuroprotective role against Aβ toxicity via activation of GAL 2 .…”

Elevated galanin may predict the risk of type 2 diabetes mellitus for development of Alzheimer’s disease

“…These findings indicate that the actived GalR2/3 may involved in the protective effects against hippocampal Aβ aggregation(Cheng and Yu, 2010;Cui et al, 2010;Elliott-Hunt et al, 2011;Pirondi et al, 2010).Further studies demonstrated the ability of galanin to improve spatial memory impairment and to decrease hippocampal Aβ levels via activation of GalR2(Elliott-Hunt et al, 2007Li et al, 2013). On one hand, the levels of galanin and GalR2 mRNA were increased significantly in the hippocampus after Aβ administration, whereas GalR1 mRNA and protein levels were not changed(Li et al, 2013).…”

“…35) induced caspase-3 mRNA expression and cell death were abolished in the presence of 10 nM galanin (2-11) in mouse SN56 cholinergic cell line(Pirondi et al, 2010). These findings indicate that the actived GalR2/3 may involved in the protective effects against hippocampal Aβ aggregation(Cheng and Yu, 2010;Cui et al, 2010;Elliott-Hunt et al, 2011;Pirondi et al, 2010).Further studies demonstrated the ability of galanin to improve spatial memory impairment and to decrease hippocampal Aβ levels via activation of GalR2(Elliott-Hunt et al, 2007Li et al, 2013).…”