Learning and memory deficits and alzheimer's disease-like changes in mice after chronic exposure to microcystin-LR

Jing Wang, Yabing Chen, Changliang Zhang, Zou Xiang, Jie Ding, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

9 Citations (Scopus)

Abstract

Previous studies have demonstrated that toxins produced by toxic cyanobacterial blooms are hazardous materials. Although microcystin-LR (MC-LR) has been revealed to inflict damage to the brain, the mechanisms underlying its neurotoxicity as a result of chronic exposure to MC-LR are not fully described. In this study, the mice were exposed to MC-LR dissolved in drinking water at doses of 1, 7.5, 15, or 30 μg/L for 180 days. MC-LR accumulated mostly in the mouse hippocampus (55 ng/g dry weight) followed by cortex (28 ng/g dry weight) after exposure to MC-LR at 30 μg/L. MC-LR exposure at this concentration induced dysfunction of learning and memory, accompanied with apoptosis of neuronal cells (with 10% reduction of the neurons in the CA1 region and 15% in the CA2 region), reduction of spine density, accumulation of β-amyloid plaques 1–42 (Aβ1-42), and enhanced phosphorylation of tau (p-tau) in the brain, which is characteristic of Alzheimer's disease (AD). These data indicate that MC-LR may induce AD-like pathology. Following prolonged exposure, MC-LR significantly upregulated the ratio of proBDNF to BDNF by downregulating the tPA levels, thereby activating downstream signaling pathways to improve the expression of p-JNK, and c-Jun while to inhibit the expression of p-Creb and p-PKC. This study uncovered new molecular mechanisms that account for neurotoxicity after chronic exposure to MC-LR, which has wide-ranging implications for public health.

Original languageEnglish
Pages (from-to)504-518
Number of pages15
JournalJournal of Hazardous Materials
Volume373
DOIs
Publication statusPublished - 5 Jul 2019

Keywords

  • Alzheimer's disease-like changes
  • Learning and memory deficits
  • Microcystin-LR
  • Water contamination

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution
  • Health, Toxicology and Mutagenesis

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