Stereological Study Of The Cholinergic Neurons In The Hippocampus Of Early-Stage APP/PS1 AD Transgenic Mouse

PART ONE THE BEHAVIORAL CHANGES OF EARLY-STAGE APP/PS1 ALZHEIMER'S DISEASE TRANSGENIC MOUSEObjective To study the behavioral changes of early-stage APP/PS1 Alzheimer's disease transgenic mouse and provide theoretical bases for further studying the morphological changes in the progress of AD.Methods Twelve 10-month-old female APP/PS1 AD transgenic mice(APP/PS1 group)and twelve age-matched littermate wild-type female mice(Wild-type group)were used.The spatial learning and memory abilities were tested with Morris water maze.In the first six days,the escape latency was recorded by the positioning of the navigation experiment;in the seventh day,the times of the platform location crosses and time spending in the target quadrant were recorded.After Morris water maze test,seven mice from each group were selected.The cerebral hemispheres were draw out after anesthesia and infusion,and one hemisphere was randomly selected form each mouse brain.After being dehydrated,the selected hemispheres were cut at 50 ?m consecutive sections with cryoultramicrotome.The sections containing hippocampus were sampled in a systematic,random fashion,and five series of sections per animal were obtained.One series of the sections were randomly selected to be used to analyze amyloid plaques in the hippocampus.Results The escape latency time of the APP/PS1 group was significantly longer than that of the Wild-type group(P < 0.01).There were significant differences in the times of the platform location crosses and the time spending in the target quadrant between the Wild-type group and the APP/PS1 group(P = 0.007,P = 0.041).The Wild-type group had no A?-ir plaques and the APP/PS1 group had a large number of A?-ir plaques in the hippocampus.Conclusions In the 10-month-old female APP/PS1 AD transgenic mice,the spatial learning and memory ability was significantly decreased,which was accompanied with a large number of A?-ir plaques in the hippocampus.PART TWO THE CHANGES OF THE HIPPOCAMPUS AND THE CHOLINERGIC NEURONS OF THE HIPPOCAMPUS IN THE EARLY-STAGE APP/PS1 ALZHEIMER'S DISEASE TRANSGENIC MOUSEObjective To investigate the early changes of the cholinergic neurons in the hippocampus of the APP/PS1 double AD transgenic mouseMethods After Morris water maze test,seven mice from each group were selected.The cerebral hemispheres were draw out after anesthesia and infusion,and one hemisphere was randomly selected form each mouse brain.After being dehydrated,the selected hemispheres were cut at 50 ?m consecutive sections with cryoultramicrotome.The sections containing hippocampus were sampled in a systematic,random fashion,and five series of sections per animal were obtained.One series of the sections were randomly selected to be used to estimate the hippocampal sub-regions volume and the number of the cholinergic neurons in the hippocampus.Results The volume of the DG and the number of the cholinergic neurons in the DG were significantly reduced in the APP/PS1 group when compared to the Wild-type group(P = 0.01,P = 0.017).The volume of the CA1 and CA2/3 fields and the number of the cholinergic neurons in the CA1 and CA2/3 fields were not significantly changed in the APP/PS1 group when compared to the Wild-type group(P =0.089,P = 0.059,P =0.076,P =0.074).Conclusions The volume of the DG and the number of the cholinergic neurons in the DG of 10-month-old female APP/PS1 transgenic AD mice were significantly reduced.The loss of the cholinergic neurons in the DG might be one of the morphological bases for the behavior deficits of the early-stage APP/PS1 AD transgenic mouse...