The role of regulatory T cells on the activation of astrocytes in the brain of high-fat diet mice following lead exposure. (5th January 2022)

• Record Type: Journal Article
• Authors: Wu, Lei; Li, Shuang; Li, Chao; He, Bin; Lv, Linyi; Wang, Jia; Wang, Jierui; Wang, Weixuan; Zhang, Yanshu
• Is Part Of: Chemico-biological interactions. Volume 351(2022)
• Publication Date: 2022-01-05
• Subjects: Lead -- High-fat diet -- Regulatory T cells -- Astrocytes -- Neuroinflammation -- Hippocampus; ATRA all-trans retinoic acid -- cDNA complementary DNA -- CNS central nervous system -- DAPI 4′, 6-diamidino-2-phenylindole -- GFAP glial fibrillary acidic protein -- HFD high-fat diet -- IP intraperitoneal injection -- MWM Morris water maze -- Pb lead -- PBS phosphate-buffered saline -- qPCR quantitative polymerase chain reaction -- qRT-PCR quantitative reverse transcription polymerase chain reaction -- SD standard deviation -- Treg cells regulatory T cells; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109740
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Lead (Pb) exposure can cause damage to the central nervous system (CNS)*. Pb can accumulate in the hippocampus, leading to learning and memory impairments. Recent studies have shown that high-fat diet (HFD) is also associated with cognitive impairment. However, there are few reports on CNS damage due to HFD and Pb exposure. We aimed to investigate the effect of Pb on cognitive functions of HFD-fed mice, focusing on the role of regulatory T (Treg) cells in astrocyte activation. C57BL/6J mice were randomly divided into control, HFD, Pb, and HFD + Pb groups. TGF-β and IL-10 secreted by Treg cells and the intracellular transcription factor Foxp3 were evaluated as a measure of Treg cell function; astrocyte activation was assessed by evaluating glial fibrillary acidic protein (GFAP) expression. The learning and memory ability was significantly lower in the HFD + Pb group than in other groups. The brain Treg cell ratio was significantly decreased and the protein levels of TGF-β, IL-10, and Foxp3 were significantly lower, whereas the protein level of GFAP was higher in the HFD + Pb group. The hippocampus of the HFD + Pb group mice showed significantly higher levels of neurotoxic reactive astrocyte markers and astrogliosis was also much higher compared to HFD and Pb groups. Furthermore, all-trans retinoic acid treatment increased the brain Treg cell ratio, reversed cognitive decline, and suppressed astrocyte activation in the HFD + Pb group mice. We concluded that HFD along with Pb exposure could aggravate the activation of astrocytes in the brain, and the brain Treg cells may be involved in inhibiting astrocyte activation in HFD-fed mice exposed to Pb. Highlights: HFD along with Pb exposure exacerbates learning and memory impairment. HFD along with Pb exposure aggravates astrocyte activation in the brain. HFD along with Pb exposure reduces the brain Treg cell ratio. Enhancing the brain Treg cell ratio could suppress astrocyte activation.