Aluminum-Induced Cognitive Impairment and PI3K/Akt/mTOR Signaling Pathway Involvement in Occupational Aluminum Workers.
Adult
Aluminum
/ toxicity
Animals
Cell Death
Cognitive Dysfunction
/ chemically induced
Female
Humans
Learning
/ drug effects
Male
Memory
/ drug effects
Mental Status and Dementia Tests
Metallurgy
Middle Aged
Neurons
/ drug effects
Neuropsychological Tests
Occupational Exposure
Phosphatidylinositol 3-Kinases
/ drug effects
Proto-Oncogene Proteins c-akt
/ drug effects
TOR Serine-Threonine Kinases
/ drug effects
Zebrafish
Aluminum
Mild cognitive impairment
Neurobehavioral toxicology
Occupational aluminum exposure
PI3K/Akt/mTOR
Journal
Neurotoxicity research
ISSN: 1476-3524
Titre abrégé: Neurotox Res
Pays: United States
ID NLM: 100929017
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
18
03
2020
accepted:
25
05
2020
revised:
20
05
2020
pubmed:
9
6
2020
medline:
16
6
2021
entrez:
8
6
2020
Statut:
ppublish
Résumé
Epidemiological studies indicate that long-term occupational exposure to aluminum (Al) causes neurotoxicity and cognitive impairment. While the molecular underpinnings associated with workers' cognitive impairment is unclear, one mechanism may involve Al-induced PI3K/Akt/mTOR activation and neuronal cell death, which impairs learning and memory in rats. Here, we sought to determine whether PI3K/Akt/mTOR is also associated with cognitive impairment in Al-exposed occupational workers. Cognitive function was screened by Mini-Mental State Examination (MMSE) and Clock-Drawing Test (CDT), and serum Al and PI3K/Akt/mTOR-associated gene expression was quantified. A negative correlation between serum Al and scores of MMSE and CDT was found, which might relate with downregulation of PI3K/Akt/mTOR. To determine the role of the PI3K/Akt/mTOR pathway cognitive function, we treated zebrafish with Al and observed a profound impairment in learning and memory. Increased brain Al levels was associated with decreased expression of PI3K/Akt/mTOR in Al-exposed zebrafish. Finally, rapamycin, an mTOR inhibitor, was added to isolate the role of mTOR specifically in the Al exposed zebrafish. The results suggested that Al induces learning and memory deficits by downregulating PI3K, Akt, and mTOR1 expression and inducing neuronal cell death like rapamycin group. This study indicates that aluminum exposure can cause cognitive impairment through PI3K/Akt/mTOR pathway, with mTOR activity being a critical player involved in this mechanism. Future studies are necessary to further characterize the role of PI3K/Akt/mTOR1 signaling in Al-induced neurocognitive decline among Al occupational workers. These findings draw attention to Al risk exposure among occupational workers and the need to implement novel safety and protective measures to mitigate neurocognitive health risks in the Al industrial workspace.
Identifiants
pubmed: 32506341
doi: 10.1007/s12640-020-00230-z
pii: 10.1007/s12640-020-00230-z
doi:
Substances chimiques
Aluminum
CPD4NFA903
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
344-358Subventions
Organisme : General Programs of National Natural Scientific Foundation of China
ID : 81673142
Organisme : General Programs of National Natural Scientific Foundation of China
ID : 81872599
Organisme : Key Program of National Natural Scientific Foundation of China
ID : 81430078
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