Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats

Abstract

Androgen loss is an important clinical concern because of its cognitive and behavioral effects. Changes in androgen levels are also suspected to contribute to neurological disease. However, the available data on the effects of androgen deprivation in areas of the brain that are central to cognition, like the hippocampus, are mixed. In this study, morphological analysis of pyramidal cells was used to investigate if structural changes could potentially contribute to the mixed cognitive effects that have been observed after androgen loss in males. Male Sprague–Dawley rats were orchidectomized or sham-operated. Two months later, their brains were Golgi-impregnated for morphological analysis. Morphological endpoints were studied in areas CA3 and CA1, with comparisons to females either intact or 2 months after ovariectomy. CA3 pyramidal neurons of orchidectomized rats exhibited marked increases in apical dendritic arborization. There were increases in mossy fiber afferent density in area CA3, as well as robust enhancements to dendritic structure in area CA3 of orchidectomized males, but not in CA1. Remarkably, apical dendritic length of CA3 pyramidal cells increased, while spine density declined. By contrast, in females overall dendritic structure was minimally affected by ovariectomy, while dendritic spine density was greatly reduced. Sex differences and subfield-specific effects of gonadal hormone deprivation on the hippocampal circuitry may help explain the different behavioral effects reported in males and females after gonadectomy, or other conditions associated with declining gonadal hormone secretion.

Sex differences in hippocampal area CA3 pyramidal cells

“…Ovariectomized females exhibited decreased spine density compared to sham females (Mendell et al 2016) consistent with previous observations in females (Woolley 2007; Luine 2016). In contrast, dendritic spine length and Sholl analysis did not reveal differences in groups (Mendell et al 2016). Therefore, the major differences in area CA3 pyramidal cells between intact and gonadectomized females were in pyramidal cell spine density, but the greatest changes between intact and gonadectomized males were in the mossy fiber axons and pyramidal cell dendritic length (Figure 4).…”

“…In addition, dendritic spine density, length and Sholl analysis of pyramidal cell dendrites were conducted. These experiments confirmed and extended the view that males and females are very different regardless of gonadectomy - they cannot be viewed as polar opposites regardless of the way the comparison is made (Mendell et al 2016). …”

“…These data support previous electrophysiological findings that this pathway was potentiated in orchidectomized males (Skucas et al 2013). In addition, the total length of the apical dendritic tree was longer in orchidectomized males than sham rats (Mendell et al 2016). In contrast, dendritic spine density and spine length did not differ extensively, but there was a significant reduction in spine density after orchidectomy (Mendell et al 2016).…”

“…In addition, the total length of the apical dendritic tree was longer in orchidectomized males than sham rats (Mendell et al 2016). In contrast, dendritic spine density and spine length did not differ extensively, but there was a significant reduction in spine density after orchidectomy (Mendell et al 2016). These changes are summarized in Figure 4.…”

“…Interestingly, the differences in ovariectomized and sham females were mostly in spine density, not mossy fibers, nor dendritic length (Mendell et al 2016); Figure 4). Ovariectomized females exhibited decreased spine density compared to sham females (Mendell et al 2016) consistent with previous observations in females (Woolley 2007; Luine 2016). In contrast, dendritic spine length and Sholl analysis did not reveal differences in groups (Mendell et al 2016).…”