苯并[a]芘暴露对小鼠嗅觉功能的毒性作用OA

[Background]Studies have shown that benzo(a)pyrene(BaP)exhibits neurotoxicity and can induce cognitive dysfunction.Olfactory dysfunction is an early marker of mild cognitive impairment;however,the mechanism by which BaP exposure causes this impairment is still unclear. [Objective]To investigate the effects of BaP exposure on olfactory function in mice. [Methods]Thirty 5-month-old male C57BL/6 mice were randomly assigned to five groups(n=6 per group):blank control,solvent control(olive oil),and low,medium and high doses(0.72,1.44,and 2.89 mg·kg-1,respectively).Following one week of acclimatization,BaP was administered in-tranasally every other day.Behavioral changes were assessed using the buried food test and Morris water maze(MWM).Olfactory bulb tissues were subsequently harvested for analysis.Hematoxylin-eosin(HE)staining was used to evaluate pathological changes,while immunofluo-rescence and quantitative polymerase chain reaction(qPCR)were employed to examine the ex-pression and distribution of protein and mRNA expressions and distributions of olfactory marker protein(OMP),membrane-spanning 4-pass A1(MS4A1),trace amine-associated receptor1(TAAR1). [Results]The buried food test revealed that BaP exposure significantly prolonged the time taken to find food in a dose-dependent manner(F=56.753,P<0.01).MWM results showed significant main effects for both time(F=128.5,P<0.01)and dose(F=3.889,P<0.05),with a sig-nificant interaction effect between them(F=2.128,P<0.05).HE staining showed that in the 2.89 mg·kg-1 group,although granule remained abundant,mitral cell layer neurons exhibited structural atrophy and deep staining.Immunofluorescence demonstrated a decreased dis-tribution of OMP,MS4A1,and TAAR1 in the olfactory nerve layer and glomerular layers in the 2.89 mg·kg-1 group compared with the blank control group(F=11.590,P<0.01;F=12.807,P<0.01;F=7.436,P<0.01).Furthermore,mRNA expression levels of OMP,MS4A1,and TAAR1 in the 2.89 mg·kg-1 group were also significantly downregulated compared to the control group(F=6.720,P<0.01;F=16.931,P<0.01;F=48.060,P<0.01). [Conclusion]BaP exposure leads to olfactory dysfunction in mice by inducing pathological damage to mitral cells and reducing the ex-pression of key olfactory receptors and markers in the olfactory bulb.