Rapid increase of spines by dihydrotestosterone and testosterone in hippocampal neurons: Dependence on synaptic androgen receptor and kinase networks

• Published in: Brain research 2015-09, Vol.1621, p.121-132
• Main Authors: Hatanaka, Yusuke, Hojo, Yasushi, Mukai, Hideo, Murakami, Gen, Komatsuzaki, Yoshimasa, Kim, Jonghyuk, Ikeda, Muneki, Hiragushi, Ayako, Kimoto, Tetsuya, Kawato, Suguru
• Format: Article
• Language: English
• Subjects: Androgen; Androgen receptor; Androgens - pharmacology; Androgens - physiology; Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiology; Dendritic Spines - drug effects; Dendritic Spines - physiology; Dihydrotestosterone; Dihydrotestosterone - pharmacology; Hippocampus; Male; MAP Kinase Signaling System; Neurology; Rats; Rats, Wistar; Receptors, Androgen - physiology; Spine; Synapse; Synapses - drug effects; Synapses - physiology; Testosterone; Testosterone - pharmacology; Testosterone - physiology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2014.12.011

Abstract Rapid modulation of hippocampal synaptic plasticity by locally synthesized androgen is important in addition to circulating androgen. Here, we investigated the rapid changes of dendritic spines in response to the elevation of dihydrotestosterone (DHT) and testosterone (T), by using hippocampal slices from adult male rats, in order to clarify whether these signaling processes include synaptic/extranuclear androgen receptor (AR) and activation of kinases. We found that the application of 10 nM DHT and 10 nM T increased the total density of spines by approximately 1.3-fold within 2 h, by imaging Lucifer Yellow-injected CA1 pyramidal neurons. Interestingly, DHT and T increased different head-sized spines. While DHT increased middle- and large-head spines, T increased small-head spines. Androgen-induced spinogenesis was suppressed by individually blocking Erk MAPK, PKA, PKC, p38 MAPK, LIMK or calcineurin. On the other hand, blocking CaMKII did not inhibit spinogenesis. Blocking PI3K altered the spine head diameter distribution, but did not change the total spine density. Blocking mRNA and protein synthesis did not suppress the enhancing effects induced by DHT or T. The enhanced spinogenesis by androgens was blocked by AR antagonist, which AR was localized postsynaptically. Taken together, these results imply that enhanced spinogenesis by DHT and T is mediated by synaptic/extranuclear AR which rapidly drives the kinase networks. This article is part of a Special Issue entitled SI: Brain and Memory.