Long-term Effects Of Reversible Olfactory Impairment On Learning And Memory In Mice And The Expression Of AD-like Molecular Proteins

Olfactory system plays an important role in our life.Smell transmits information to the olfactory bulb through binding with the odorant receptors,and then to other brain regions.Most of these brain regions are r elated to cognitive processing.Alzheimer’s disease is a complex neurodegenerative disease,which seriously affects cognition and memory.Its pathological characteristics are extracellular amyloid plaque deposition and intracellular nerve fiber entanglement.Olfactory impairment occurs earlier than cognitive impairment in AD.Olfactory impairment is closely related to the pathological degree of AD.Pathological changes includs olfactory bulb atrophy and neuron loss in AD.Olfactory dysfunction leads to memory impairment,elevated tau protein phosphorylation level and Aβaccumulation in the brain,which replicates AD characteristics.Our previous study found that after the reversible olfactory dysfunction caused by the destruction of olfactory epithelium.The olfactory ability of mice had recovered at one month,but the learning and memory of mice had been damaged for a long time.To explore whether reversible olfactory dysfunction is related to the pathogenesis of AD,t his study further studied the learning and memory,tau protein phosphory lation level and the change of Aβin related brain regions of mice 3,6 and 9 months after the reversible olfactory dysfunction.The results are as follows:1、Single reversible olfactory dysfunction did not affect the anxiety like behavior of mice in the open field,but the mice showed obvious anti anxiety like behavior at 1and 3 months after olfactory dysfunction in the elevated plus maze.The exercise ability of mice in the two experiments was sig nificantly higher than that in the control group.2、One month,three months and six months after a single reversible olfactory dysfunction,the memory of mice with olfactory dysfunction decreased in the Y-maze,but only the mice with olfactory dyfunction for six months showed impairment of learning ability in the fear condition,and there was no significant difference in the process of memory extraction.3、Western blotting showed that the phosphorylation level of tau protein in olfactory bulb increased in 3 and 6 months after single zinc sulfate treatment,and the phosphorylation level of tau protein increased only 3 months after treatment in hippocampus.The results of ELISA showed that the concentration of Aβ_{1-4 0} was lower than that in the control group in olfactory bulb 9 month,and Aβ_{1-4 2} in the olfactory bulb 3 months after single reversible olfactory dysfunction.The concentration of Aβ_{1-4 2} was significantly higher than that in the control group in hippocampus 3 and 6 months after dysfunction.4、Multiple reversible olfactory dysfunctions did not affect the anxiety like behavior of mice in the open field,but the mice showed obvious anti anxiety like behavior at6 and 9 months after olfactory dysfunction in the elevated plus maze.The exercise ability of mice in the two experiments was significantly higher than that in the control group.5、In the multiple reversible olfactory dys functions,the space recognition memory of the experimental group and the control group in the Y-maze decreased at 3 and 6months,and the space recognition memory of the Y-maze recovered at 9 months.The learning and memory of all mice in the fear condition were not affected.Conclusion:The cognitive ability decreased and the phosphorylation level of tau protein increased and the concentration of Aβchanged in 3 and 6 months after a single olfactory dysfunction.These changes simulate the important characteristics of AD.There are risk factors that may lead to reversible olfactory loss in our daily living environment,such as metal exposure,air pollution,formaldehyde exposure,viral cold and so on.This study provides a basis for the relationship between olfactory dysfunctions and the pathogenesis of AD,that is,reversible olfactory dysfunction in life may lead to the changes of cell molecules and functions in various brain regions of olfactory pathway,and ind uce or aggravate the pathogenesis of AD.