title: Amelioration of β-amyloid-induced cognitive dysfunction and hippocampal axon degeneration by curcumin is associated with suppression of CRMP-2 hyperphosphorylation.
abstract: The Alzheimer's disease (AD) brain is characterized by β-amyloid deposition, hyperphosphorylation of microtubule-associated proteins, formation of senile plaques and neurofibrillary tangles, and degeneration of specific neuronal populations. Collapsin response mediator protein 2 (CRMP-2) hyperphosphorylation has been implicated in AD-associated neural process regression and neurofibrillary tangle formation. Curcumin is a promising AD drug with incompletely defined therapeutic mechanisms. One possibility is that curcumin prevents β-amyloid-induced CRMP-2 hyperphosphorylation, thereby protecting against axonal regression and (or) promoting axonal regrowth. We examined spatial learning in the Morris water maze, hippocampal expression levels of CRMP-2 and phosphorylated CRMP-2 (p-CRMP-2) by Western blot, and NF-200 (an axon-specific marker) by immunohistochemistry in Sprague-Dawley rats subjected to a single intrahippocampal injection of Aβ1-40 alone or Aβ1-40 followed by curcumin (i.p. daily for 7 days). Compared to controls, spatial learning was significantly impaired in these Aβ1-40-injected AD model rats (P<0.05). In addition, hippocampal expression levels of CRMP-2 and NF-200 were reduced while p-CRMP-2 expression was significantly enhanced (P<0.05 for all). Overexpression of p-CRMP-2 was correlated with NF-200 underexpression (r(2)=-0.67308, P<0.05), suggesting that Aβ1-40 damaged hippocampal axons. Spatial learning deficits were reversed, CRMP-2 and NF-200 expression levels increased, and p-CRMP-2 expression reduced in curcumin-treated rats (all P<0.05). We propose that curcumin improves spatial learning by inhibiting CRMP-2 hyperphosphorylation, thus protecting against β-amyloid-induced hippocampal damage or promoting regeneration.
authors.affiliation: Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China. Electronic address: wangyunliangmedsci@163.com.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Wang
authors.forename: Honglei
authors.initials: H
authors.lastname: Yin
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Zhilei
authors.initials: Z
authors.lastname: Zeng
authors.forename: Nana
authors.initials: N
authors.lastname: Qiao
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Cui
authors.forename: Jiyu
authors.initials: J
authors.lastname: Lou
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D003474:Curcumin / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C095114:collapsin response mediator protein-2; D003474:Curcumin
keywords: Alzheimer's disease; Amyloid β protein; Axon; CRMP-2; Curcumin