Galanin protects amyloid-beta-induced neurotoxicity on primary cultured hippocampal neurons of rats.

The neuropeptide galanin and its receptors are found to be upregulated in brain associated with Alzheimer's disease (AD), while the role of galanin in AD is still unclear. The present study was performed to explore the neuroprotective role of galanin both in vitro and in vivo. Our results demonstrated that galanin inhibited the neurotoxicity induced by amyloid-beta(25-35) (Abeta(25-35)) or Abeta(1-42) in primary cultured hippocampal neurons of rats. Moreover, Gal(2-11) (an agonist of GalR(2/3)) also inhibited the neurotoxicity induced by Abeta(25-35) in the cultured neurons. We further found that galanin inhibited the activation of p53, Bax, and caspase-3 induced by Abeta(25-35) in the cultured hippocampal neurons. Moreover, galanin reversed the down regulation of Bcl-2 induced by Abeta(25-35) in the cultured neurons. Interestingly, in the Morris water maze task we found that intra-CA1 injection of Abeta(25-35)-induced spatial learning deficits in rats were blocked by galanin. In addition, galanin inhibited the Abeta(25-35)-induced dysregulation of p53, Bax, and MAP2 in rat hippocampus. Our results strongly demonstrate that galanin plays neuroprotective roles in nerve cells and in AD-induced learning and memory deficits.