Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome.

Xiao Li Zhang; Sheng Nan YU; Ruo Di QU; Qiu Yi Zhao; Wei Zhe Pan; Xu Shen Chen; Qian Zhang; Yan Liu; Jia LI; Yi Gao; Yi Lyu; Xiao Yan Yan; Ben LI; Xue Feng Ren; Yu Lan Qiu

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Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome.

Author: Xiao Li ZHANG ^{1
,

2} ; Sheng Nan YU ³ ; Ruo Di QU ³ ; Qiu Yi ZHAO ³ ; Wei Zhe PAN ³ ; Xu Shen CHEN ⁴ ; Qian ZHANG ³ ; Yan LIU ³ ; Jia LI ³ ; Yi GAO ³ ; Yi LYU ³ ; Xiao Yan YAN ³ ; Ben LI ³ ; Xue Feng REN ^{5
,

6} ; Yu Lan QIU ³
Author Information

1. Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China
2. Department of Microbiology Laboratory, Linfen Central Hospital, Linfen 041000, Shanxi, China.
3. Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
4. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo 14214, New York, USA.
5. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo 14214, New York, USA
6. Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo 1421, New York, USA.
Publication Type:Journal Article
Keywords: Arsenic; Fluoride; Learning and memory impairment; Metabolome; Microbiome
MeSH: Rats; Animals; Arsenic/toxicity*; Fluorides; RNA, Ribosomal, 16S/genetics*; Rats, Sprague-Dawley; Metabolome; Microbiota
From: Biomedical and Environmental Sciences 2023;36(3):253-268
CountryChina
Language:English
Abstract: OBJECTIVE:Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).
METHODS:We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.
RESULTS:Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.
CONCLUSION:Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.