Effects of testosterone on synaptic plasticity mediated by androgen receptors in male SAMP8 mice.
Synaptic changes are closely associated with cognitive deficits. In addition, testosterone (T) is known to exert regulative effects on synaptic plasticity. T may improve cognitive deficits in Alzheimer's disease (AD) patients, but the underlying mechanisms of androgenic action on cognitive performance remain unclear. The aim of this study was thus to examine the protective mechanism attributed to T on cognitive performance in an AD senescence, accelerated mouse prone 8 (SAMP8) animal model. Using Golgi staining to quantify the dendritic spine density in hippocampal CA1 region, molecular biomarkers of synapse function were analyzed using immunohistochemistry and western blot. T significantly increased the dendritic spine density in hippocampal CA1 region, while flutamide (F) inhibited these T-mediated effects. Immunohistochemistry and western blot analysis showed that the expression levels of brain derived neurotrophic factor (BDNF), postsynaptic density 95 (PSD-95), and p-cyclic-AMP response element binding protein (CREB)/CREB levels were significantly elevated in the T group, but F reduced the T-induced effects in these biomarkers to control levels. There were no significant differences in the expression levels of PSD-95, BDNF, and p-CREB/CREB between C and F. These findings indicate that the effects of T on improvement in synaptic plasticity were mediated via androgen receptor (AR). It is conceivable that new treatments targeted toward preventing synaptic pathology in AD may involve the use of androgen-acting drugs.
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Jian-Xin
JX
Jia
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Cheng-Li
CL
Cui
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Xu-Sheng
XS
Yan
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Bai-Feng
BF
Zhang
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Wei
W
Song
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Dong-Sheng
DS
Huo
b School of Health Sciences , University of Newcastle , Newcastle , Australia.
He
H
Wang
a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.
Zhan-Jun
ZJ
Yang
D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000235:genetics* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D000076122:Disks Large Homolog 4 Protein; D005485:Flutamide / Q000494:pharmacology; D015870:Gene Expression; D051528:Guanylate Kinases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D011897:Random Allocation; D011944:Receptors, Androgen / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology
D059002:Androgen Receptor Antagonists; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D011944:Receptors, Androgen; D013739:Testosterone; D005485:Flutamide; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051528:Guanylate Kinases