Format

Send to

Choose Destination
Brain Behav Immun. 2018 Jul;71:66-80. doi: 10.1016/j.bbi.2018.04.014. Epub 2018 Apr 26.

Tau hyperphosphorylation and P-CREB reduction are involved in acrylamide-induced spatial memory impairment: Suppression by curcumin.

Author information

1
Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China.
2
School of Public Health, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, PR China.
3
Department of Nutrition and Food Hygiene, MOE Key Lab of Environment and Health, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
4
Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong-Road, Wuhan 430030, PR China. Electronic address: yanhong@mails.tjmu.edu.cn.

Abstract

Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser262), AT8 (p-tau Ser202/Thr205) and PHF1 (p-tau Ser396/404) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity.

KEYWORDS:

Acrylamide; CREB reduction; Curcumin; PERK- eIF2α- ATF4; Spatial memory impairment; Tau phosphorylation

PMID:
29704550
DOI:
10.1016/j.bbi.2018.04.014
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center