| Objective: Observe the effect castration and androgen replacement therapy on hippocampal synaptic plasticity in senescence accelerated mouse-prone/8(SAMP8). Further investigate the effect of androgen to improve mechanism of synaptic plasticity and to provide some experimental proof.Methods: Twenty-one 6-month-old male SAMP8 were randomly divided into sham-operation control group(P8 group), castrated group, and androgen replacement therapy with castrated group(DHT group) ( 7 in each group).Choose seven 6-month-old males SAMR1 as normal contrast of the consanguinity group(R1 group). Castrated group and DHT group were removed twin testis. DHT group hypodermic injection 1mg/(kg·day)DHT after 1day. Other groups were injected equal asepsis medical maize oil, 1 time/day , 21days altogether.Tissue preparation and staining observation: 7 mice of every group were taken out, broken right auricle and perfused quickly with normal saline and subsequently fixed with 4% paraform via left ventricle. From superior colliculus to optic chiasma segment, the brain made the same two parts through middle sagittal viewing by razor blade. One was made use for Golgi staining, the other was made of paraffin sections using for HE staining, Nissl staining, anti-synaptophysin immunohistochemical staining, anti- N-methyl -D-aspartate receptor 1(NMDAR1)immunohistochemical staining and negative control.Results:1. With HE staining, neurons in hippocampal CA1 region of R1 group were well-arranged, with clear stratification. While neurons in P8 group were slightly deranged, cellular layers also decreased. And neurons in castrated group presented diffuse vacuolar degeneration, swollen, sparsely and disorderedly arranged, with cell nucleuses karyochrome and pyknosis. Compared with castrated group, neurons in hippocampal CA1 region of DHT group lessen the pathological lesion obviously .2. With Nissl staining, neuronal Nissl bodies in hippocampal CA1 region of R1 group were rich and dense, with statistical difference (P<0.01), while the neuronal Nissl bodies in the P8 group were fairly sparse. Neurons in hippocampal CA1 region of castrated group were much fewer and presented karyopyknosis, turbidness and anachromasis, with less and even dissolved Nissl bodies. The neuron number in hippocampal CA1 region of DHT group increased, with significantly statistical difference comparing with castrated group(P<0.05), but no statistical difference comparing with P8 group(P>0.05).3. with Golgi staining, the dendritic spines in hippocampal CA1 region of R1 group were morphology regulation ,well-arranged and intensive, the number of the apical dendritic thorns density was 1.36±0.18 piece/μm, with statistical difference comparing with others group (P<0.01);the number of the apical dendritic thorns density of hippocampal CA1 region of castrated group was decreased obviously(0.94±0.19 piece/μm). The number of dendritic spine of DHT group increased(1.13±0.15 piece/μm), with significantly statistical difference comparing with castrated group(P<0.05), but no statistical difference comparing with P8 group(1.16±0.11 piece/μm)(P>0.05).4. With anti- synaptophysin immunohistochemistry, the average optical density values of the castrated group (0.077±0.025)was significantly lower than others (P<0.05). While the optical density valued in DHT group ( 0.096±0.012 ) were obviously increaser than those in the castrated group(P<0.05).5. With anti-NMDAR1 immunohistochemistry, the average optical density values of the castrated group(0.045±0.017) was significantly lower than the P8 group(0.057±0.016) and the DHT group(0.061±0.015) (P<0.05). The P8 group and DHT group have no significant difference(P>0.05). Conclusions:1. Androgen deficiency after castrating in SAMP8 results in hippocampal neurons sparse and disordered,swollen and degenerated,the morphosis damaged, the number of withered neurons increase, and many neurons lost. Androgen replacement can improve the pathological lesion and lessen the apoptosis and loss of hippocampal neurons.2. Androgen deficiency after castrating in SAMP8, in hippocampus CA1 region ,the density of dendritic thorns decrease obviously and protein level of the synaptophysin reduce. Androgen replacement therapy can increase the density of dendritic thorns , raise protein level of the synaptophysin and modulated synaptic plasticity of hippocampal CA1 region.3. Androgen deficiency after castrating in SAMP8 results in the protein level of the NMDAR1 markedly decreased, Androgen replacement therapy can raise the protein level, it may turn out that DHT potentially affect hippocampal synaptic plasticity by modulating pyramidal cell NMDAR1.
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