Testosterone has sublayer-specific effects on dendritic spine maturation mediated by BDNF and PSD-95 in pyramidal...

Testosterone has a number of important physiological roles and acts on peripheral target tissues and the central nervous system. Testosterone exerts many of its effects through the androgen receptor (AR). ARs are widely distributed in nervous tissues and particularly strongly expressed in hippocampal CA1 pyramidal neurons, which play critical roles in spatial memory tasks. Dendritic spines are specialized to receive synaptic inputs, and a change in spine morphology is correlated with the strength and maturity of each synapse. In this study, we used thy1-GFP transgenic male adult mice to analyze the morphology of dendritic spines in the hippocampal CA1 area. Gonadectomy (GDX) induced aberrant morphologies with less mushroom-type and more stubby- and thin-type spines in the proximal part of the stratum radiatum after two weeks. These morphological changes were also observed in the distal part of the stratum radiatum, whereas there was no change in the stratum lacunosum-moleculare after GDX. Testosterone replacement in GDX mice recovered the changes in spine types to those found in controls. To determine the mechanism of the testosterone-dependent morphological changes, we examined expression of brain-derived neurotrophic factor (BDNF) and its downstream target post-synaptic density protein 95 (PSD-95). GDX induced a significant decrease in the protein levels of BDNF and PSD-95 in the CA1 area, which were prevented by testosterone replacement. These findings reveal a novel role of testosterone in prevented the differential response properties of spine maturation in sublayers of dendritic spines in the CA1 area via the actions of BDNF and PSD-95.