The Study On The Relationship Between Arnt2and Npas4Expressions And Cognitive Impairment In The Hippocampus Of Post-stroke Depression Rats

BackgroundPost-stroke depression (PSD) is a frequent post-stroke mood disorder. The cognitive impairment is a commom symptom of PSD. The depression greatly affected the recovery of nerve function and the life quality by interacting in PSD patients’cognitive impairment. Aryl hydrocarbon receptor nuclear translocator2(ARNT2) and neuronal PAS domain protein4(NPAS4) are the transcription factors in the hippocampus. They expressions might influence the emotion change and cognitive function of PSD patients by regulating and controlling the function of brain-derived neurotrophic factor (BDNF).Objectives1To study the expression of ARNT2and NPAS4in the hippocampus of PSD rats and understand the expression pattern of ARNT2-NPAS4regulated BDNF in the hippocampus of PSD rats.2To understand the relationship between ARNT2and NPAS4expressions and cognitive impairment and explore the possible mechanisms of the ARNT2and NPAS4expressions involved in the process of PSD cognitive impairment.Methods1The focal cerebral ischemic rat model is set up by occluding the middle cerebral artery (MCA). On this basis, further isolated-living condition and chronic unpredictable mild stress (CUMS) are applied successively to set up the PSD rat model.2The neurological functional impairment of focal cerebral ischemic rats is assessed by Longa Five grades. To observe the weight variation trend by measuring the rats weights, sucrose solution consumption test is used to estimate the interest and cheerfulness, open field test (OFT) is used to detect the spontaneous activities and self-explored behavior. The purpose is to evaluate the depressive symptoms of models.3Expression of ARNT2in the hippocampus of models is detected by using immunohistochemistry technique. Expressions of ARNT2and NPAS4mRNA in the hippocampus of models are detected by using reverse transcription-polymerase chain reaction (RT-PCR). To explore the relationship between ARNT2and NPAS4expressions and cognitive impairment in the PSD rats.Results1①The rats weight growth trends of the PSD group and the depression group are slow. After the models bulid, the differences have statistical significance (F=18.864, P=0.000) compared with the normal control group. There is no statistical significance between the PSD group and the depression group (P>0.05).②After the models bulid, the decreases of sucrose solution consumption test for the PSD group (P<0.01) and the depression group (P<0.05) have statistical significance (F=8.766, P=0.000) compared with the normal control group. There is no statistical significance between the PSD group and the depression group (P>0.05).③The horizontal movement and vertical motion of the PSD group and the depression group are significantly reduced compared with the normal control group, the differences have statistical significance (FOFT horizontal movement=5.216, POFT horizontal movement=0.005; FOFT vertical motion-6.951,POFT vertical motion=0.001;POFT horizontal movement<0.05, POFT vertical motion <0.01). There is no statistical significance between the PSD group and the depression group (P>0.05).2The average optical density values of ARNT2protein in the hippocampus of PSD and stroke groups are higher than the normal control group, the differences have statistical significance (FCA1=14.248, PCa1=0.000; FCA2=14.374,PCA2=0.000; FCA3=17.569, PCA3=0.000).3①The ARNT2mRNA relative expression are significantly increased in the hippocampus of the PSD group (P<0.01) and the stroke group (P<0.05), the differences have statistical significance (F=7.887, P=0.001) compared with the normal control group. There is no statistical significance between the PSD group and stroke group (P>0.05). No statistical significance exist in the depression group and the normal control group (P>0.05).②The NPAS4mRNA relative expression are significantly decreased in the hippocampus of the PSD group (P<0.05) and the depression group (P<0.01), the differences have statistical significance (F=7.223, P=0.001) compared with the normal control group. No statistical significance exist in the depression group and PSD group (P>0.05).There is no statistical significance between the stroke group and the normal control group (P>0.05).4There is no correlation between the relative expression of ARNT2and NPAS4in the hippocampus of PSD rat model.Conclusions1The upregulated expression of ARNT2in the hippocampus of PSD rat model closely related to the ischemic injury of brain, but its relationship with cognitive impairment remains to be explored.2The decreased expression of NPAS4in the hippocampus of PSD rat model may involvement in the biologic mechanisms of cognitive impairment.