Galanin attenuates beta-amyloid (Abeta) toxicity in rat cholinergic basal forebrain neurons.
In brains of Alzheimer's disease (AD) patients, expression of the neuropeptide galanin is significantly upregulated and galanin-immunoreactive fibers hypertrophy and hyperinnervate cholinergic neurons of the basal forebrain. However, the role of galanin in AD, whether it is detrimental or neuroprotective, remains controversial. In this study, using primary cultured neurons from the rat basal forebrain, we show that pretreatment with galanin protects cholinergic neurons against beta-amyloid-induced apoptotic cell death as judged by visual observation, MTT assay, Live/dead cell assay, TUNEL and cleaved caspase-3 staining. These effects are mimicked by the galanin receptor 2 (GALR2) agonist, AR-M1896. Western blot analysis revealed Abeta-induced decrease in phospho-PKC and phospho-Akt levels was reversed by galanin. Galanin also attenuated cleavage of caspases-3 and -9 following exposure to Abeta. These findings support a neuroprotective role for galanin and may have implications for development of compounds based on this peptide to treat AD.
Ding
Xiling
X
Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
MacTavish
David
D
Kar
Satyabrata
S
Jhamandas
Jack H
JH
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D019004:Galanin / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009410:Nerve Degeneration / Q000517:prevention & control; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D044092:Receptor, Galanin, Type 2 / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D044092:Receptor, Galanin, Type 2; C434734:galanin (2-11)-amide; D019004:Galanin; D000109:Acetylcholine