Aluminum-Induced Cognitive Impairment and PI3K/Akt/mTOR Signaling Pathway Involvement in Occupational Aluminum Workers.

Abstract

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.

• Authors: Nan Shang, Ping Zhang, Shuo Wang, Jianping Chen, Rong Fan, Jin Chen, Tao Huang, Yanhong Wang, Jeremy Duncan, Ling Zhang, Qiao Niu, Qinli Zhang
• Journal: Neurotoxicity research (Neurotox Res) Vol. 38 Issue 2 Pg. 344-358 (Aug 2020) ISSN: 1476-3524 [Electronic] United States
• PMID: 32506341 (Publication Type: Journal Article)

Chemical References

• Aluminum
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Adult
• Aluminum (toxicity)
• Animals
• Cell Death
• Cognitive Dysfunction (chemically induced, metabolism)
• 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, metabolism)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)
• TOR Serine-Threonine Kinases (drug effects, metabolism)
• Zebrafish