The Expression And Function Of Tau Protein In Rat Neurodegeneration Caused By Infrasound

Background: Infrasound is a sound wave which in the ears outside the range of frequency less than 20 Hz.There are a lot of infrasound in nature?earthquake,tsunami etc?and human social life and production activities?wind power generation,rocket launch,the ship launched a manned spacecraft,etc.?.Infrasound likes a lot of audible sounds widely exists,but it cannot be shielded and protected by physical means effectively.The effect of infrasound on CNS?Central nervous system?has been a hot research topic.Previous research found: 8Hz,130 dB infrasound exposure after 4 weeks,the number of cells having the ability of proliferation in hippocampal DG region decreased significantly compared with the control group;we also found that animal's spatial cognition was damaged in water maze test.In addition,infrasound of certain parameters exposure would cause many changes in the CNS,including cerebral cortex and hippocampus ultrastructure,cholinergic neurons in brain cells,expression of Ca²⁺ NOSmRNA and ion distribution,the expression of iNOSmRNA and GFAP in the hippocampus.It can be seen that infrasound can cause a wide range of brain damage,abnormal neuronal ultrastructure,decreased levels of neurotrophic factors,leading to neurodegeneration and cognitive impairment,etc..Infrasound exposure has a significant effect on CNS,so that it must be a serious threat to astronauts,military activities and other related professionals physical and mental health.Therefore,it is necessary and urgent to further study the mechanism of infrasound induced neurodegeneration and cognitive impairment.Objective: Most of studies believe that biological resonance mode is an important way that infrasound act on human's various tissues and organs.It is known that the natural frequency of the human brain is about 8Hz.When the frequency of infrasound is 8Hz,it will affect the CNS by the way of biological resonance.The study found: low intensity infrasound cause headache,dizziness,inability to concentrate,emotional fear;long time high intensity infrasound can result in insanity,madness,shock,convulsions,phrenoplegia until death.The above mentioned symptoms are attributed to the disorder of the nervous system and the degeneration of the nerve.However,the cause of the acoustic nerve network system disorders,and even lead to neurodegenerative disease,is still a mystery.There are many studies about Tau protein in AD and other neurodegeneration and cognitive dysfunction disease,and also relatively mature.Based on our previous experimental results,we hypothesized that high intensity infrasound exposure will be through the excessive increase of Tau protein and phosphorylated Tau in the central nervous system,causing nerve degeneration and cognitive function disorder.Therefore,in-depth study and exploring the mechanism of Tau protein led to the process of neurodegeneration and cognitive impairment in the neural molecular,seeking for the accurate and effective target of drug therapy after the infrasound exposure.It will have very important significance to improve the anti-injury and repair the compensatory ability of the brain.Methods :?1?Building a model of infrasound exposure in rats,8Hz,130 dB infrasound,daily 2 hours irradiation at the beginning.After the infrasound exposure,some rats were perfused into the hearts and stripped of brain tissue.The brain tissues were fixed,dehydrated,embedding in wax block.Others were obtained hippocampus tissues by acute isolation.Then,we will extract the protein and supernatant tissue of rat hippocampus,obtained brain tissue sections.We use Tunel staining,Western-blot?WB?and immunohistochemistry,Elisa to detect the influence of infrasound on apoptosis of hippocampus in rats,and explore the changes of Tau protein and P-Tau?phosphorylated Tau protein?expression in rat hippocampus.?2?Setting up a same model as before,8Hz,130 dB infrasound,daily 2 hours' irradiation.After the infrasound exposure,rats were perfused into the hearts and stripped of brain tissue.The brain tissues were fixed,dehydrated,embedding in wax block.We used immunofluorescence to detect the expression of Phosphorylation of CaMKII in rat hippocampus.?3?Setting up a drug intervention measure and giving rats intraperitoneal injection the antagonist of Ca²⁺ before the rat infrasound exposure 1 hour ago.Using immunohistochemical staining method to detect the expression of Tau protein and P-Tau?phosphorylated tau protein?in rat hippocampal after giving the antagonist of Ca²⁺.Results:?1?For a long time?7d,14d?infrasound exposure with 8Hz,130 dB parameter,we found that it may promote apoptosis of hippocampal neurons.The number of apoptotic cells was different from that in control group?P<0.05?,by using TUNEL staining.The expression of Tau Protein in hippocampus has a growing trend,and the expression of Tau protein in 14 d group is the most significant.7d group have more expression of Tau Protein than 1d group and control group?p<0.05?,14 d group have more expression of Tau Protein than 7d group?p<0.05?,1d group and control group have no the otherness?p>0.05?.For a long-term?14d?infrasound exposure,one hour to six hours the expression of Tau is the most significant,twenty-four hours later the expression of Tau has some recovery,but it is still strongly than control group?p<0.05?.The expression of P-Tau in 7d group and 14 d group was higher than that in control group?p<0.05?,and the difference between 14 d group and 7d group was statistically significant?p<0.05?.?2?8Hz,130 dB infrasound exposure,the expression of pT286-CaMKII is most significant in the hippocampus after 14 d infrasound exposure,it is stronger than 7d,1d and control group?p<0.05?.?3?The results showed that the method of intraperitoneal injection of calcium blockers did not reduce the expression of Tau protein and P-Tau protein in the hippocampus.The expression of Tau protein and P-Tau protein in hippocampus increased with the increase of irradiation time.Conclusion:8Hz,130 dB infrasound exposure,the expression of Tau protein and P-Tau protein increased in hippocampus of rats.The increasing of Tau protein and P-Tau protein,especially P-Tau protein may be associated with infrasound exposure rat neurodegeneration and learning and memory impairment.