Effects of short-chain fatty acids on cognitive impairment induced by benzo[a]pyrene in mice
Objective To investigate the effects of short-chain fatty acids(SCFAs)on the cognitive function,cerebral cortex,and colon of mice chronically exposed to benzo[a]pyrene(B[a]P),and to explore the underlying mechanisms.Methods Thirty 8-week-old male ICR mice were randomly divided into control group,B[a]P group,and B[a]P+SCFAs group,with 10 mice in each group.The B[a]P group was intragastrically given B[a]P at a dose of 10.0 mg/kg every other day for 45 times,while the control group was given an equal volume of peanut oil,with free access to purified water for both groups.The B[a]P+SCFAs group was ex-posed to B[a]P at 10.0 mg/kg and at the same time,which was provided with a SCFAs solution(67.5 mmol/L sodium acetate,40 mmol/L sodium butyrate,and 25.9 mmol/L sodium propionate)for drinking.After exposure,the variation of cognitive function of the mice was tested using the T-maze test,novel location recognition test,hole-board test,and pole test.The pathological changes in the cortex and colon were observed with HE staining.The expression levels of the inflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the cortex and colon were determined by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of the tight junction proteins zonula occluden-1(ZO-1)and occludin in the colon were measured using RT-PCR and Western blot,respectively.Results Compared with the control group,the B[a]P group showed significantly decreased spa-tial memory and motor ability and significantly increased anxiety-like responses(P<0.05),suggesting the occurrence of cognitive dys-function;developed a large number of red neurons in the brain,disorganized intestinal cells,incomplete and sparse intestinal villi,and reduced and unevenly distributed goblet cells;showed significantly increased IL-1β levels(P<0.05)and insignificantly increased ex-pression of TNF-α in the cortex and colon(P>0.05);and showed significant reductions in the mRNA and protein expression of ZO-1 and occludin in the colon(P<0.05).Compared with the B[a]P group,the B[a]P+SCFAs group showed significantly improved spa-tial memory and motor ability and significantly resolved anxiety-like responses(P<0.05),suggesting that SCFAs could significantly al-leviate B[a]P-induced cognitive dysfunction in mice;at the same time,SCFAs significantly reduced the number of red neurons in the brain,recovered the number of goblet cells in the colon,significantly decreased IL-1β levels in the cortex and colon and TNF-α levels in the cortex(P<0.05),and significantly upregulated the mRNA and protein expression of ZO-1 and occludin in the colon(P<0.05).ConclusionSCFAs treatment can effectively improve B[a]P-induced cognitive dysfunction in mice,which may be through in-creasing the mRNA and protein expression of tight junction proteins in the colon,reducing intestinal permeability,promoting the repair of the intestinal mucosal barrier,and thus alleviating intestinal and neural inflammation.
short-chain fatty acidsbenzo[a]pyrenecognitive impairmentinflammatory factorintestinal tight junction protein
NETL
NSTL
万方数据
