The Change Of Recognitive Function And Its Relationship To White Matter Damage In Aged Rats

Objective:The significant character of brain aging is the damage of recognitive function.Up to now,its mechanism is unknown.There are not effective methods of prevention and treatment.In the past several years,the basic and clinical researchs have already confirmed that white matter damage was an important cause of the decline of recognitive function.It was often seen that the white matter change resulted the decline of recognitive function in clinic.The essential component of white matter are gliacyte,myelin sheath and axon. Protein Lipid Protein(PLP)is an important component of myelin sheath.Adhesion molecule,Contactin-associated protein(Caspr),in paranode of Ranvier node,is the important molecule that maintains the function of myelin sheath and axon.Their Changes may result in structural and functional changes of myelin and axon.Furthermore,they affect white matter function.This thesis studied changes of learning and memory function, the structural and functional change of white matter in aged rats in four aspects.(1) In behavioral aspect,the changes of recognitive function was studied in aged rats;(2) the change of central conductive function during brain aging;(3) PLP expressive changes; (4)The expressive and functional change of Caspr2 between myelin and axon and its relationship with the damage of axon and myelin sheath.The purpose is to reveal the effect of aging on recognitive function and the significance of axon and myelin sheath changes.Methods:The wistar rats were divided into two groups:young group(6-7 months) and aged group(18-24 months).Morris water maze was adopted to evaluate learning and memory function of rats.The conductive latency time of perforant pathway was recorded by Electrophysiological methods to evaluate central conductive function of forebrain regions in rats.Transmission electron microscope(TEM) was used to observe the ultramicrostructural changes of white matter in rats,such as myelin sheath and axon. Immunohistochemistry techniques was applied to detect expressive changes of PLP and adhesion molecule Caspr2 in brain aging.LEICA QWIN image analytical system was used to analyze integrated optical density(IOD) of PLP immunostaining.Results:1.The escape latency increased significantly in aged group rats than young group(P＜0.01).The mean percentage(%)of path in the 95%central zone were significantly lower in the aged group(P＜0.01),the first time passing hidden platform prolonged significantly in the aged group(P＜0.05).In the obvious platform experiment,escape latency significantly delayed in aged group than young group(P＜0.05).2.The central conductive time increased significantly in aged group than young group(P＜0.01).3.In the ultramicrostructural changes of white matter,axon diameter increased,which contained megamitochondrion.The structure of mitochondrion was vague,ridge was disaggregated.The dense granule was observed in aged groups.The gaps around enlarged. In myelin sheath,the compact layer separated and some layers structure of myelin were confused,destructed.It can be seen that electron density increased and lipofuscin deposited in cytoplasm of gliacyte.4.In PLP Immunohistochemistry,it had been seen positive staining in striatum, callosum,anterior commissure,subcortex regions in two groups.But the PLP expressive capacity decreased obviously and IOD value(optical density value) increased obviously in aged group than young group(P＜0.01).5.In Caspr2 immunofluorescence staining,positive fluorescent staining were seen in two groups.It showed points and strips in green fluorescence.Fluorescent staining intensity decreased obviously in aged group than young group.Conclusions:1.In aged group rats,not only the spatial reference learning and memory function but also the memory maintenance function significantly decreased than young group rats.2.The conductive latency time of perforant pathway prolonged in brain aging,which showed that central conductive function decreased.It was probably relevant to the decline of learning and memory function in aged group rats.3.There were significant changes of ultramicrostructure in oligodendrocyte,myelin sheath and axon,which may be an important reason of the decline of white matter function during brain aging.4.The expression of PLP decreased,that is relevant to the morphological and structural changes of myelin sheath.This change probably have some relation with the decline of conductive function and the damage of recognitive function during brain aging.5.Expression of Caspr2,an adhesion molecule between myelin and axon,decreased in brain aging.It resulted in separation between myelin sheath and axon.Furthermore,it affected structure and function of white matter.It has an important rank in the damage of white matter during brain aging.