Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Age-Dependent Sensitivity to the Neurotoxic Environmental Metabolite, 1,2-Diacetylbenzene

  • Hoang, Ngoc Minh Hong (Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Kim, Sungjin (Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Nguyen, Hai Duc (Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Kim, Minjo (Molecular Inflammation Research Center for Aging Intervention (MRCA), Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Kim, Jin (Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University) ;
  • Kim, Byoung-Chul (Systems Toxicology Research Center, Korea Institute of Toxicology) ;
  • Park, Daeui (Systems Toxicology Research Center, Korea Institute of Toxicology) ;
  • Lee, Sujun (Department of Pharmacology, College of Medicine, Inje University) ;
  • Yu, Byung Pal (Department of Physiology, The University of Texas Health Science Center at San Antonio) ;
  • Chung, Hae Young (Molecular Inflammation Research Center for Aging Intervention (MRCA), Department of Pharmacy, College of Pharmacy, Pusan National University) ;
  • Kim, Min-Sun (Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University)
  • Received : 2020.11.16
  • Accepted : 2021.02.10
  • Published : 2021.07.01
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Abstract

1,2-Diacetylbenzene (DAB) is a metabolite of 1,2-diethylbenzene, which is commonly used in the manufacture of plastics and gasoline. We examined the neurotoxic effects of DAB in young and old rats, particularly its effects on hippocampus. Previously, we reported DAB impairs hippocampal neurogenesis but that the underlying mechanism remained unclear. In this study, we evaluate the toxicities exhibited by DAB in the hippocampi of 6-month-old (young) and 20-month-old (old) male SD rats by treating animals intraperitoneally with DAB at 3 mg/kg/day for 1 week. Hippocampal areas were dissected from brains and RNA was extracted and subjected to RNA-seq analysis. RNA results showed animals exhibited age-dependent sensitivity to the neurotoxic effects of DAB. We observed that inflammatory pathways were up-regulated in old rats but that metabolism- and detoxification-related pathways were up-regulated in young rats. This result in old rats, especially upregulation of the TREM1 signaling pathway (an inflammatory response involved in Alzheimer's disease (AD)) was confirmed by RT-PCR. Our study results provide a better understanding of age-dependent responses to DAB and new insight into the association between DAB and AD.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant from the Korean government (MEST) (grant nos. NRF2013R1A1A3008851 and 2018R1D1A1B07049610).

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