Abstract
Gonadal hormones can modulate brain morphology and behavior. Recent studies have shown that hypogonadism could result in cortical function deficits. To this end, hormone therapy has been used to ease associated symptoms but the risk may outweigh the benefits. Here we explored whether genistein, a phytoestrogen, is effective in restoring the cognitive and central neuronal changes in late middle age and surgically estropause female rats. Both animal groups showed poorer spatial learning than young adults. The dendritic arbors and spines of the somatosensory cortical and CA1 hippocampal pyramidal neurons were revealed with intracellular dye injection and analyzed. The results showed that dendritic spines on these neurons were significantly decreased. Remarkably, genistein treatment rescued spatial learning deficits and restored the spine density on all neurons in the surgically estropause young females. In late middle age females, genistein was as effective as estradiol in restoring spines; however, the recovery was less thorough than on young OHE rats. Neither genistein nor estradiol rectified the shortened dendritic arbors of the aging cortical pyramidal neurons suggesting that dendritic arbors and spines are differently modulated. Thus, genistein could work at central level to restore excitatory connectivity and appears to be potent alternative to estradiol for easing aging and menopausal syndromes.
Highlights
Dendrites, the primary sites of synaptic inputs in central neurons, are dynamic structures whose arbors and spines change in normal situation upon environmental changes [1], hormonal fluctuation [2] and aging [3,4,5,6], and in addition in response to injuries [7,8,9,10], and diseases [11]
Blood estrogen analysis showed that the level of estrogen in all young adult OHE animals was below detectable whether they were treated with genistein or vehicle
We examined the effect on the dendritic spines of CA1 pyramidal neurons of the dorsal hippocampus because they are reported to be involved in spatial memory acquisition
Summary
The primary sites of synaptic inputs in central neurons, are dynamic structures whose arbors and spines change in normal situation upon environmental changes [1], hormonal fluctuation [2] and aging [3,4,5,6], and in addition in response to injuries [7,8,9,10], and diseases [11]. Phytoestrogens are plant compounds that exert estradiollike physiological effects in both humans and rats [18,19] They received a great deal of attention as alternatives of estradiol for the potential preventive roles against some of today’s most prevalent hypogonadism-associated chronic diseases, such as cardiovascular disease, osteoporosis and hormone-related cancers [20,21,22]. These estrogen-like molecules are found in many plants and are especially abundant in soy products [18].
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