title: Effects of dihydrotestosterone on synaptic plasticity of hippocampus in male SAMP8 mice.
abstract: The senescence-accelerated-prone mouse 8 (SAMP8) has been proposed as a suitable, naturally derived animal model for investigating the fundamental mechanisms of Alzheimer's disease (AD). In addition, the serum testosterone levels decrease quickly in the natural growth process of this model. This study investigated the effect of androgen deficiency on the synaptic plasticity of hippocampus in male SAMP8 mice after castration and dihydrotestosterone (DHT) administration. We observed the dendritic spines and synapses using Golgi staining and transmission electron microscope. Androgen deficiency after castration significantly reduced the number of apical dendritic thorns, and the abnormal ultrastructure of excitatory synapses was more obvious. Androgen replacement therapy reversed this change. To explore the protective mechanisms and neurological basis of DHT, we researched the changes of expression of GluN1 subunit-containing N-methyl-D-aspartate receptors (NMDARs) and synaptophysin (SYN), which are closely related to synaptic plasticity. Comparisons were made among results observed with immunohistochemistry techniques, Western blots analysis and RT-PCR analysis. The GluN1 and SYN regulation at the protein and mRNA levels probably be related to the DHT-induced morphological synaptic plasticity. This study will be helpful for understanding the function of androgen, and it provides a valuable theoretical basis about the protective and therapeutic targets of androgen in AD.
authors: Department of Human Anatomy, Hebei Medical University, Shijiazhuang 050017, PR China.
authors: Sha
authors: S
authors: Li
authors: Lin
authors: L
authors: Kang
authors: Chao
authors: C
authors: Zhang
authors: Guosheng
authors: G
authors: Xie
authors: Nan
authors: N
authors: Li
authors: Yu
authors: Y
authors: Zhang
authors: Juan
authors: J
authors: Du
authors: Huixian
authors: H
authors: Cui
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000728:Androgens / Q000172:deficiency; D000818:Animals; D023902:Chromosome Pairing / Q000187:drug effects* / Q000502:physiology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009919:Orchiectomy; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D000728:Androgens; C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; D013196:Dihydrotestosterone
keywords: Castration; Dihydrotestosterone; Hippocampus; SAMP8; Synaptic plasticity