Effect Of Dihyudrostestosterone On Synaptic Ultrastructure Of Hippocampus In SAMP8

Objective:Observe the effect castration and androgen replacement therapy on hippocampal synaptic ultrastructure in senescence accelerated mouse-prone/8(SAMP8). Further investigate the mechanism of androgen to improve synaptic ultrastructure.Methods:Fifteen 6-month-old male SAMP8 were randomly divided into sham-operation control group(P8 group), castrated group, and androgen repla-cement therapy with castrated group(DHT group).Choose five 6-month-old male SAMR1 as normal contrast of the consanguinity group(R1 group). Castr-ated group and DHT group were removed twin testis. DHT group,hypodermic injection 1mg/(kg·day) dihydrotestosterone(DHT) after 1 day. Other groups were injected equal asepsis medical maize oil,1 time/day,21 days altogether.Tissue preparation and staining observation:Broke right auricle and perfused quickly with normal saline, subsequently fixed with 3% paraform and 1% glutaral via left ventricle. From superior colliculus to optic chiasma segment, through middle sagittal viewing, the brain was separated into two parts by razor blade. One was used for Golgi staining to survey dendritic spine density, the other was used for transmission electron microscope observation and to analyze the excitatory synaptic numerical density(Nv), surface density(Sv) and average thickness of postsynaptic dense material(Dv) in hippocampal CA1 region by stereology.Results:Golgi staining results:R1 group's CA1, CA3 area of the hippocampus two-three level dendritic spines density respectively for 1.40±0.19a/μm, 1.71±0.38a/μm, higher than the other group (P<0.01). P8 group's CA1, CA3 area of respectively 1.17±0.18a/μm,1.46±0.41a/μm; CA1, CA3 area of DHT respectively 1.11∧0.15a/μm,1.35±0.19a/μm; P8 group and DHT group density similar(P<0.05), it is less than R1 group, castration group's CA1, CA3 area of respectively0.72±.16a/μm,1.03±0.26a/μm, compared to other group density minimum(P<0.05).Transmission electron microscope and stereology analysis results:R1 gr-oup's the hippocampus CA1 area radiation layer excitability synaptic number density Nv, surface density Sv, average thickness of postsynaptic dense mater-ial Dv respectively 0.14±0.02a/μm3,0.51±0.10μm2/μm3,51.3±10.9nm, each value are higher than the other group (P<0.01). P8 group CA1 area synaptic Nv, Dv, Sv. Respectively 0.10±0.01a/μm3,0.36±0.02μm2/μm3,31.8±8.7nm; DHT group Nv, Sv, Dv respectively 0.09±0.02a/μm3,0.33±0.06μm2/μm3,28.8±9.7nm, P8 group and DHT group all have similar(P>0.05), Were less than R1 group. group Castration group Nv, Sv, Dv for 0.07±0.01a/μm3,0.19±0.03μm2/μm3,22.8±5.8nm, compared to other group density minimum (P<0.05).Conclusions:1 SAMP8 as an excellent animal model for research AD(Alzheimer's disease), Their poor learning and memory abilities were associated with the lower number and the abnormal ultrastructure of excitatory synapse in hippocampal CA1 region.Removed twin testis, the lower number and the abnormal ultrastructure of excitatory synapses in SAMP8 hippocampal CA1 region would be more obvious.2 Androgen replacement therapy could improve the number of castrated SAMP8 hippocampal excitatory synapse and thicken their postsynaptic dense (PSD). The curative mechanism of androgen might be related to enhancing synaptic morphological plasticity of hippocampal neurons.