Changes In The Expression Of NT3 And TrkC In The Hippocampus Of Alzheimer Disease Rats Induced By Amyloid B-Peptide_25-35

Objective:(1): To testify the viability and repeatability of Alzheimer disease (AD) model induced by injecting β-amyloid protein into bilateral hippocampus of rats.(2): To demonstrate the changes of expression of NT3 and trkC in hippocampal neurons of AD model rats induced by amyloid β-peptide_25-35 (Aβ_25-35).(3): To investigate the mechanism of NT3 and trkC involved in the pathogenesis of AD.Methods:Thirty male Wistar rats were randomly divided into control and model groups. AD model was established stereotaxically by injecting amyloid β-peptide25-35 (Aβ25-35) into bilateral hippocampus of rat, while control-group rats were injected with normal saline at the same site. All rats were tested with Morris water maze for memory and learning function two weeks after injection. Then the two group rats were killed at the same time and hippocampal microstructure were observed by optic microscope. The expressions of NT3 and trkC were then detected by immunohistochemical method(SABC).Results: 1. Results of rats behaviorMorris water maze test was used to detect the learning and memory function of the rats. In Morris water maze, the average escape latency of AD-model rats in the platform at the navagation subtest was obviously longer than the control-group rats. The number of platform-crossings within 120s in AD-model rats at the space-exploration subtest was fewer than in control-group rats. Both the two subtest's results showed of statistical significance (P<0.01).2. Observation of hippocampus pathological specimen of rats.By HE staining, fewer hippocampal neurons in CA1-CA4 regions with condense chromatin in nucleus were observed in model group, while the hippocampal neurons of control-group rats showed normal sized nucleus and staining.The arrangement of the hippocampal neurons in CA1 subregion in control group was more orderly than in model group.3. The expression of NT3 and trkC in hippocampus of rats:Different expression level was present between NT3 and trkC in the different subfields of the hippocampus. The number of NT3 imunoreactive neurons within hippocampal subfield CA1 , CA2 and CA3 in model group was obviously reduced compared with control group (P < 0.01), while no difference was found in CA4 and hilar subfield between the two groups (P > 0.05); No difference in the number of trkC imunoreactive neurons in each hippocampal subfield between the two groups was observed (P > 0.05).Conclusions:(1): The AD model induced by injecting p-amyloid protein into bilateral hippocampus of rats could imitate well the changes of behaviour and pathology of AD.(2): The decrease of expression of NT3 nor its receptor's down-regulation in hippocampus was associated with AD model rats' leaning and memory dysfunction, suggesting exogenous NT3-supply may counteract the neurotoxcity of β amyloid protein. The relationship of trkC and AD need to further demonstrate.(3): Different expression level was present between NT3 and trkC in the different subfields of AD-model rats' hippocampus. The experiment's results can provide morphological evidence for further investigation of the mechanism of NT3 and trkC involved in the pathogenesis of AD.