The Effect And Mechanism Of TPHP Exposure On Anxiety And Depression-like Behaviors In Rats

Objective: To investigate the neurotoxic effect and mechanism of TPHP exposure on anxiety and depression-like behaviors in rats.Methods:Respective fifty-two healthy male and female SD rats were divided randomly into four groups,including the solvent(corn oil)control group,TPHP exposure groups at three doses of low(50 mg/kg),medium(100mg/kg)and high(250 mg/kg).Rats were treated with TPHP or solvent by oral gavage at a fixed time daily for 60 days consecutively,and their body weight were measured once a week.At the end of administration,the anxiety-like behaviors of animals were tested via open field test and the depression-like behaviors were evaluated via forced swimming test and novelty suppressed feeding test.The pathological changes of prefrontal cortex were observed by hematoxylin-eosin(HE)staining under a microscope.The cortical protein levels of BDNF/Trk B/CREB signal pathway were determined by Western blotting method.Results: In the open field test,the retention time and distance within the center of the male rats exposed to TPHP were reduced compared with the control group(P<0.05);but there is no difference in female groups(P>0.05).In the forced swimming test and novelty suppressed feeding test,the immobility time,and the latency to feeding in male groups of TPHP exposure were significantly increased compared to control group(P<0.05),but there is no significant difference found among the female groups(P>0.05).The cortical neurons were swollen,degenerated,and necrotic in the TPHP treated male groups,while no difference was found in female groups.The results of Western blot showed the expressions of BDNF and TrKB proteins were significantly decreased in dose-dependent manner(P<0.05)in male rats exposed to TPHP.The levels of CREB were significantly decreased in the male groups of TPHP exposure compared with the control group,and the medium and high dose groups were significantly decreased than the low dose group(P<0.05).There was no difference in the expressions of BDNF,TrKB and CREB in the female groups(P>0.05).Conclusions:1.TPHP exposure may cause sex-specific anxiety and depression-like behaviors in rats,anxiety and depression-like behaviors were found in male rats,while no significant effects were found in female rats.2.The potential mechanism underlying the anxiety and depression-like behaviors in animals is possibly related with the BDNF/Trk B/CREB pathway in the prefrontal cortex.