Effects Of Chronic Noise On MRNA And Protein Expression Of CRF Family Molecules And Its Relationship With P-tau In The Rat Hippocampus And PFC

With the development of modern industrial society,the harm of noise is becoming more and more serious.Traffic,social life,industry and some special environmental noise affect people's work,study and life all the time.WHO document indicated that noise pollution has become an increasingly serious social and public health problem,in addition to damage the auditory system,but also can cause a variety of health problems,especially the nervous system injury is a research hotspot in recent years.The results of laboratory research study showed that long-term noise exposure can cause AD-like changes(Alzheimer 's disease,AD),such as persistent tau hyperphosphorylation and accumulation of A? in hippocampus and prefrontal cortex(PFC)in rats,but the specific mechanism of injury is not clear.Corticotropin releasing factor(CRF)system plays a key role in the abnormal phosp horylation of tau protein caused by non-noise stress stimulation.The purpose of this paper is to study the possible molecular mechanism of the abnormal phosphorylation of tau protein in hippocampus and PFC of rats induced by long-term noise exposure.Taking CRF as the breakthrough point,to explore the effects of noise exposure on the gene and protein expression of C RF system,and orientation relation of CRF a nd p-tau in hippocampus and PFC.To provide a theoretical basis for further understanding the mecha nism of neurodegeneration induced by noise and preventive measures.?Objective?To explore the effects of chronic noise exposure on the CRF system in the hippocampus and PFC of rats and its relationship to AD-like changes such as tau phosphorylation.In order to deeply understand the signal mechanism of AD like changes caused by long-term noise exposure,and to provide theoretical basis for targeted prevention of AD like nervous system lesion caused by noise exposure.?Methods?64 male Wistar rats were randomly divided into control and noise exposure groups,each containing 32 rats.Animals in the noise-exposed group were placed in an environment with 95 dB sound pressure level white noise,4 hours/day × 30 days,the control group had the same treatment conditions with exposed group except receiving noise;Rats were restored 0,3,7,14 days respectively after the final exposure.At different time points(days 0,3,7,or 14)after the final exposure,rats in the noise-exposed and control groups were sacrificed,six rats from each time point and group were used for ELISA,RT-PCR,and western blot analyses,furthermore,plasma was collected from abdominal aorta and plasma corticosterone(CORT)was measured by Elisa,the expression of CRF and C RFR1,C RFR2 mRNA were detected by RT-PCR in hippocampus and PFC of rats,C RF,CRFR1,CRFR2 protein expression changes were detected by Western blot.Two rats from each time point(days 0,3,7,or 14)and group were used for immunofluorescence.Rats were deeply anaesthetized with chloral hydrate and perfused through the ascending aorta with saline followed by 4% paraformaldehyde,After perfusion,brains were removed dehydrated through a graded ethanol series and embedded in paraffin.Serial 6 mm coronal sections were cut on a microtome.Double immunofluorescence method was used to mark CRF and p-tau in hippocampus and PFC slices after the tissue sections were dewaxed,hydrated and antigen retrieval,the expression and localization of CRF and p-tau in hippocampus and PFC neurons were examined using a fluorescence microscope.?Results?1.Plasma corticosterone levelsIn our study,the level of plasma corticosterone was significantly increased after 30 days of exposure to noise,with an increasing trend that persisted up to 7 days after the cessation of exposure(P<0.05),that in the noise exposed group returned to the control group at 14 days recovery.2.Chronic noise exposure increases CRF,CRFR1,and CRFR2 expression in the hippocampus and PFCThe results showed that the expression o f CRF and C RFR1 mRNA and protein were significantly increased after 30 days of exposure to noise,with an increasing trend that persisted up to 7 days(P<0.05)after the cessation of exposure,that in the noise exposed group returned to the control group at 14 days recovery.Expression of CRFR2 exhibited a delayed upregulation that showed a robust increase in mRNA and protein levels in the noise-exposed group at days 3 and 7 after exposure(P <0.05).3.Co-localization of CRF and p-tau in the rat hippocampus and PFCTo explore the relationship between CRF and p-tau,double labelingof CRF and p-tau was performed on sections through the rat hippocampus and PFC.The results show that a high proportion of CRF cells co-localized with p-tau in the hippocampus and PFC.CRF immunoreactivity within cell bodies showed green cytoplasmic staining,and red p-tau staining was also observed in the cytoplasm,yel ow is the double staining of CRF and p-tau.?Conclusions?1.Long-term noise exposure can stimulate the body to start the HPA axis,resulting in a significant increase in plasma corticosterone in rats,makeing the body to take response to the stress stimulation.2.Long-term noise exposure can significantly affect the expression of CRF signaling system in hippocampus and PFC of rat,though there are differences in performance and mechanism;CRFR2 showed a delayed elevation phenomenon and it may be involved in the anti-inflammatory process mediated by CRFR1,which is a self protection mechanism of body.3.The co-localization of CRF and p-tau in hippocampus and PFC neurons further enhanced the possibility of C RF signaling system involved in abnormal tau phosphorylation during long-term noise exposure.