Age-Dependent Sensitivity to the Neurotoxic Environmental Metabolite, 1,2-Diacetylbenzene

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.

Senotherapeutics and Their Molecular Mechanism for Improving Aging

“…Aging is defined as a physiological dysfunction in an organism and is closely related to many chronic human diseases, including metabolic syndrome, cancer, and neurodegenerative diseases ( Campisi, 2013 ; Munoz-Espin and Serrano, 2014 ; Hoang et al ., 2021 ).…”

Prolactin and Its Altered Action in Alzheimer’s Disease and Parkinson’s Disease

“…PRL crosses the blood-brain barrier (BBB) and has strong modulatory effects on hypothalamic growth and many other brain regions [5,21,22]. PRL has been associated with immune system regulation as it has both inflammatory and anti-inflammatory effects in various NDDs [23][24][25]. Additionally, several reports indicate PRL has a role in the CNS and influences neurodegeneration [21,[26][27][28][29][30][31][32].…”