title: Aluminium chloride impairs long-term memory and downregulates cAMP-PKA-CREB signalling in rats.
abstract: Epidemiological investigations have indicated that aluminium (Al) is an important environmental neurotoxicant that may be involved in the aetiology of the cognitive dysfunction associated with neurodegenerative diseases. Additionally, exposure to Al is known to cause neurobehavioural abnormalities in animals. Previous studies demonstrated that Al impaired early-phase long-term potentiation (E-LTP) in vivo and in vitro. Our previous research revealed that Al could impair long-term memory via the impairment of late-phase long-term potentiation (L-LTP) in vivo. However, the exact mechanism by which Al impairs long-term memory has been poorly studied thus far. This study was designed not only to observe the effects of subchronic Al treatment on long-term memory and hippocampal ultrastructure but also to explore a possible underlying mechanism (involving the cAMP-PKA-CREB signalling pathway) in the hippocampus of rats.. Pregnant Wistar rats were assigned to four groups. Neonatal rats were exposed to Al by parental lactation for 3 weeks and then fed with distilled water containing 0, 0.2%, 0.4% or 0.6% Al chloride (AlCl3) for 3 postnatal months. The levels of Al in the blood and hippocampus were quantified by atomic absorption spectrophotometry. The shuttle-box test was performed to detect long-term memory. The hippocampus was collected for ultrastructure observation, and the level of cAMP-PKA-CREB signalling was examined. The results showed that the Al concentrations in the blood and hippocampus of Al-treated rats were higher than those of the control rats. Al may impair the long-term memory of rats. Hippocampal cAMP, cPKA, pCREB, BDNF and c-jun expression decreased significantly, and the neuronal and synaptic ultrastructure exhibited pathological changes after Al treatment. These results indicated that Al may induce long-term memory damage in rats by inhibiting cAMP-PKA-CREB signalling and altering the synaptic and neuronal ultrastructure in the hippocampus.
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China; Shenyang Medical College, 146 Yellow River North Street, Shenyang 110034, PR China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Lifeng
authors: L
authors: Zhang
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Cuihong
authors: C
authors: Jin
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Xiaobo
authors: X
authors: Lu
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Jinghua
authors: J
authors: Yang
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Shengwen
authors: S
authors: Wu
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China.
authors: Qiufang
authors: Q
authors: Liu
authors: Shenyang Medical College, 146 Yellow River North Street, Shenyang 110034, PR China.
authors: Rong
authors: R
authors: Chen
authors: Shenyang Medical College, 146 Yellow River North Street, Shenyang 110034, PR China.
authors: Chunyu
authors: C
authors: Bai
authors: Shenyang Medical College, 146 Yellow River North Street, Shenyang 110034, PR China.
authors: Di
authors: D
authors: Zhang
authors: Medical College, Eastern Liaoning University, 49 Jingshan Street, Dandong 118003, PR China.
authors: Linlin
authors: L
authors: Zheng
authors: 9th People's Hospital of Shenyang, 18 South 11th West Road, Shenyang 110024, PR China.
authors: Yanqiu
authors: Y
authors: Du
authors: Department of Toxicology, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China; Department of Occupational and Environmental Health, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang 110001, PR China. Electronic address: cmuycai@163.com.
authors: Yuan
authors: Y
authors: Cai
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002712:Chlorides / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008569:Memory Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D057567:Memory, Long-Term / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
chemical_list: D017607:Aluminum Compounds; D019208:Brain-Derived Neurotrophic Factor; D002712:Chlorides; D017362:Cyclic AMP Response Element-Binding Protein; D000077410:Aluminum Chloride; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Aluminium; Hippocampus; Long-term memory; Ultrastructure; cAMP-PKA-CREB