title: Detecting the presence of hippocampus membrane androgen receptors in male SAMP8 mice and their induced synaptic plasticity.
abstract: Testosterone (T), the principal androgen, and its metabolite, dihydrotestosterone (DHT), are known to mediate their effects through binding to intracellular androgen receptors (iARs). In addition to their well-known genomic effects, androgens rapidly alter neuronal excitability through a non-genomic pathway mediated by membrane androgen receptors (mARs). The existence and specificity of mARs in the hippocampus were investigated in SAMP8 mice. Using T-BSA-FITC, we detected plasma membrane labeling by flow cytometry analysis for the presence of mARs. The specificity of binding was examined with iAR antagonist or anti-iAR antibody. Flow cytometry analysis showed that pretreatment with iAR antagonist, flutamide (F), failed to completely prevent the coupling action of the T-BSA-FITC membrane binding. In addition, we found classical iARs did not localize to the membrane of hippocampal neurons. These data indicate that these mARs might be not identical to classical iARs. Modulation of hippocampal synaptic plasticity by androgen has been attracting much attention. To identify the functional consequences induced by mARs, we analyzed the rapid effects of T on the density of dendritic spines using Golgi staining. The application of 50 μg/5 μl T and 30 μg/5 μl DHT induced a rapid increase in the dendritic spines within 2 h. Almost no difference was observed between T and T-BSA in the effect on thorn density. Next, we explored the protective mechanism and found that T and DHT altered the expression of synaptophysin (SYN) and postsynaptic dense material 95 (PSD95), which play crucial roles in cognitive function and synaptic plasticity.
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China; Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Hebei, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Human Anatomy, Hebei Medical University, Hebei, PR China; Hebei Key Laboratory for Brain Aging and Cognitive Neuroscience, Hebei, PR China. Electronic address: cuihuixianky@yahoo.com.
authors.forename: Huixian
authors.initials: H
authors.lastname: Cui
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D049229:Dendritic Spines / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D000076122:Disks Large Homolog 4 Protein; D005485:Flutamide / Q000494:pharmacology; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009473:Neuronal Plasticity / Q000187:drug effects; D011944:Receptors, Androgen / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D011944:Receptors, Androgen; D016708:Synaptophysin; C569015:Syp protein, mouse; D013196:Dihydrotestosterone; D013739:Testosterone; D005485:Flutamide; D051528:Guanylate Kinases
keywords: Alzheimer's disease; Androgen; Castration; Hippocampus; Membrane androgen receptors; SAMP8; Synaptic plasticity