Selective estrogen receptor modulators regulate dendritic spine plasticity in the hippocampus of male rats

Abstract

Some selective estrogen receptor modulators, such as raloxifene and tamoxifen, are neuroprotective and reduce brain inflammation in several experimental models of neurodegeneration. In addition, raloxifene and tamoxifen counteract cognitive deficits caused by gonadal hormone deprivation in male rats. In this study, we have explored whether raloxifene and tamoxifen may regulate the number and geometry of dendritic spines in CA1 pyramidal neurons of the rat hippocampus. Young adult male rats were injected with raloxifene (1 mg/kg), tamoxifen (1 mg/kg), or vehicle and killed 24 h after the injection. Animals treated with raloxifene or tamoxifen showed an increased numerical density of dendritic spines in CA1 pyramidal neurons compared to animals treated with vehicle. Raloxifene and tamoxifen had also specific effects in the morphology of spines. These findings suggest that raloxifene and tamoxifen may influence the processing of information by hippocampal pyramidal neurons by affecting the number and shape of dendritic spines.

Figure 1

Examples of dendritic spines stained with the Golgi method. Left panel: photomicrograph of a CA1 pyramidal neuron impregnated with a modification of the Golgi method. Spines studied in the present work were counted in a segment 50 μm in length of a secondary dendrite (arrow) protruding from its parent apical dendrite. SO: stratum oriens; SP: stratum pyramidale; SR: stratum radiatum. Scale bar = 100 μm. In the right panels, photomicrographs show representative examples of thin (a), mushroom (b), stubby (c), wide (d), branched (e), and double (f) spines (arrows). Scale bar = 5 μm.