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.
Cheng
Yong
Y
Neurobiology Laboratory and National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, People's Republic of China.
Yu
Long-Chuan
LC
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D019004:Galanin / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; D019004:Galanin; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3