Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats

Abstract

The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in male rats. Gonadectomy (GDNX) had no significant effect on the number of CA1 pyramidal cells but reduced CA1 spine synapse density by almost 50% (to 0.468 +/- 0.018 spine synapses/microm(3)) compared with sham-operated controls (0.917 +/- 0.06 spine synapses/microm(3)). Treatment of GDNX rats with testosterone propionate (500 microg/d, s.c., 2 d) increased spine synapse density to levels (1.01 +/- 0.026 spine synapses/microm(3)) comparable with intact males. A similar increase in synapse density (1.013 +/- 0.05 spine synapses/microm(3)) was observed in GDNX animals after treatment with dihydrotestosterone (DHT) (500 microg/d, s.c., 2 d) but not after estradiol (10 microg/d, s.c., 2 d; 0.455 +/- 0.02 spine synapse/microm(3)). These data indicate that testosterone is important for maintenance of normal spine synapse density in the CA1 region of the male rat hippocampus. The comparable responses to testosterone and the non-aromatizable androgen DHT, coupled with the lack of response to estradiol, suggest that testosterone acts directly on hippocampal androgen receptors rather than indirectly via local estrogen biosynthesis.

Fig. 1.

Electron micrographs demonstrate identical areas on two consecutive, serial sections taken from the stratum radiatum of the CA1 subfield. a shows the reference section andb the look-up section. Only those spine synapses were counted that were seen just in one section. Long arrowspoint at the same spine, which forms synaptic contact only inb. Spine synapses that are in postsynaptic position in both sections (small arrows) and axo-dendritic synapses were not counted. D, Dendrite. Scale bar, 1 μm.

Fig. 2.

Bar graph shows the result of the unbiased stereological calculation of spine synapse density in the stratum radiatum of the CA1 subfield of control, gonadectomized (GDX), gonadectomized plus testosterone-treated (GDX+T), gonadectomized plus dihydrotesterone-treated (GDX+DHT), and gonadectomized plus estrogen-treated (GDX+E2) male rats. There is no significant difference between the density values of spine synapses between the Control, GDX+T, andGDX+DHT animals. However, the spine synapse density of the GDX and GDX+E2 rats is significantly (p < 0.001) lower (48%) than that of control animals.