Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.208
Age-Dependent Sensitivity to the Neurotoxic Environmental Metabolite, 1,2-Diacetylbenzene
Ngoc Minh Hong Hoang1, Sungjin Kim1, Hai Duc Nguyen1, Minjo Kim2, Jin Kim1, Byoung-Chul Kim3, Daeui Park3, Sujun Lee4, Byung Pal Yu5, Hae Young Chung2,* and Min-Sun Kim1,*
1Department of Pharmacy, College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Suncheon 57922,
2Molecular Inflammation Research Center for Aging Intervention (MRCA), Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241,
3Systems Toxicology Research Center, Korea Institute of Toxicology, Daejeon 34114,
4Department of Pharmacology, College of Medicine, Inje University, Busan 47392, Republic of Korea
5Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
*E-mail: minsun@scnu.ac.kr (Kim MS) , hyjung@pusan.ac.kr (Chung HY)
Tel: +82-61-750-3756 (Kim MS), +82-51-510-2814 (Chung HY)
Fax: +82-61-750-3708 (Kim MS), +82-51-518-2821 (Chung HY)
Received: November 16, 2020; Revised: January 13, 2021; Accepted: February 10, 2021; Published online: April 6, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Neurotoxicity, 1,2-Diacetylbenzene, RNA-seq, DEB, Aging


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