Chronic MC-LR exposure promoted Aβ and p-tau accumulation via regulating Akt/GSK-3β signal pathway.

Abstract

It has been reported that microcystin-leucine-arginine (MC-LR) can enter into the brain and demonstrate neurotoxicity resulting in learning and memory deficits. While, there is still a lack of clear understanding of the related molecular mechanisms. In this study, we observed β-amyloid (Aβ) accumulation and tau hyperphosphorylation (p-tau) at sites of Ser396 and Thr205 in mouse hippocampus and cortex, Alzheimer's disease (AD) like changes, after chronic exposure to MC-LR at different concentrations (1, 7.5, 15 and 30 μg/L) for 180 days. The hallmarks of AD are characterized by senile plaques and neurofibrillary tangles (NFT), with associated loss of neurons, resulting in cognitive impairment and dementia. Similarly, the production of Aβ and tau hyperphosphorylation was also detected in HT-22 cells treated with MC-LR. In addition, MC-LR promoted increased expressions of BACE1 and PS1, but reduced mRNA expressions of ADAM family members both in vivo and in vitro, promoting the Aβ production. Moreover, we identified Akt/GSK-3β signal pathway mediated the Aβ and p-tau accumulation, bringing about Alzheimer's disease-like changes. Furthermore, microglial cells were activated in those mice exposed to MC-LR. Inflammatory cytokines were also found being activated to release in vitro. In conclusion, this study could provide a clue for MC-LR-induced neurotoxicity, which gave insights into the environmental risks of Alzheimer's disease.

• Authors: Yuhan Ma, Jing Wang, Dihui Xu, Yabing Chen, Xiaodong Han
• Journal: The Science of the total environment (Sci Total Environ) Vol. 794 Pg. 148732 (Nov 10 2021) ISSN: 1879-1026 [Electronic] Netherlands
• PMID: 34323745 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• tau Proteins
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• Amyloid Precursor Protein Secretases
• Aspartic Acid Endopeptidases

Topics

• Amyloid Precursor Protein Secretases
• Animals
• Aspartic Acid Endopeptidases
• Glycogen Synthase Kinase 3
• Mice
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• tau Proteins (metabolism)