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The Journal of Neuroscience, January 14, 2004, 24(2):495-499; doi:10.1523/JNEUROSCI.4516-03.2004
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BRIEF COMMUNICATION
Androgens Increase Spine Synapse Density in the CA1 Hippocampal Subfield of Ovariectomized Female Rats
Csaba Leranth,1,2 Tibor Hajszan,1,3 andNeil J. MacLusky4 Departments of 1Obstetrics and Gynecology and 2Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8063 3Laboratory of Molecular Neurobiology, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Hungary, and 4Center for Reproductive Sciences, Columbia University Medical School, New York, New York 10032
The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female rats. Treatment of OVX rats with testosterone propionate (TP; 500 µg/d, s.c., 2 d) significantly increased spine synapse density (from 0.661 ± 0.016 spine synapse/µm3 in OVX rats to 1.081 ± 0.018 spine synapse/µm3 after TP treatment). A smaller, but still statistically significant, increase in synapse density (0.955 ± 0.029 spine synapse/µm3) was observed in OVX animals after treatment with the nonaromatizable androgen dihydrotestosterone (DHT; 500 µg/d, s.c., 2 d). Administration of 1 mg of letrozole, a powerful nonsteroidal aromatase inhibitor, 1 hr before the steroid injections almost completely blocked the synaptic response to testosterone, resulting in a mean synapse density (0.723 ± 0.003 spine synapse/µm3) only slightly higher than in OVX control rats. By contrast, the response to DHT was unaffected by letrozole pretreatment. These data suggest that androgen secretion during the female reproductive cycle may contribute to cyclical changes in hippocampal synaptic density. They also indicate that androgen treatment may be as effective as estrogen replacement in reversing the decline in hippocampal CA1 spine synapses that follows loss of ovarian function. Induction of hippocampal synapse formation by androgen is not mediated entirely via intracerebral estrogen biosynthesis, however, because aromatase-independent mechanisms also significantly affect CA1 spine synapse density.
Key words: testosterone; spine synapse density; CA1; hippocampus; unbiased stereological calculation; dihydrotestosterone
Received May 22, 2003; revised November 6, 2003; accepted November 19, 2003.
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