The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes.

Alzheimer's disease (AD) is three times more prevalent in women than men, and epidemiological studies have shown that estrogen replacement in aging women forestalls the onset of AD. Hyperphosphorylation of the tau protein that forms the neurofibrillary tangles found in AD brains might be responsible for the breakdown of microtubules in affected neurons. The mechanisms by which tau protein is phosphorylated in the AD brain are not fully understood. Using a human neuroblastoma cell line (SH-SY5Y) and primary cultures of newborn male or female rat cerebral cortical neurons, we investigated the effect of 17beta-estradiol on tau protein expression and phosphorylation. We found that estradiol increased total tau and induced dephosphorylation at the proline-directed site of the molecule. Further, estradiol prevented okadaic acid-induced hyperphosphorylation of tau in both proline- and non-proline-directed sites, and antiestrogens blocked this effect. To our knowledge, this is the first report of an effect of estradiol on naturally occurring and induced tau phosphorylation. This assumes special significance because the estrogen action was found to be sexually dimorphic in rat cortical neurons and differentiation-sensitive in human neuroblastoma cells.

Objective: To compare the efficacy of fractional CO2 laser therapy with topical estrogen therapy for the treatment of postmenopausal genitourinary syndrome of menopause. Methods: We conducted a randomized controlled clinical trial involving 25 postmenopausal women. Participants were aged between 50 and 65 years with at least 1 year of amenorrhea and follicle-stimulating hormone levels of >40 IU/L. The women were randomized into two groups: the laser therapy group (n = 13) and the vaginal topical estrogen therapy group (n = 12). Changes in the vaginal epithelium thickness, Frost index, and cell maturation were analyzed in both the groups. The female sexual quotient of each woman was also evaluated. Subjective evaluation was performed through a physical examination. Results: Histological analysis showed a significant increase in the vaginal epithelium thickness at the end of treatment in females in both the laser therapy (P < 0.001) and topical estrogen therapy (P = 0.001) groups. The topical estrogen therapy group tended to present a higher maturation index at the end of treatment when compared with that of the other group. Sexual function increased significantly over time in both the topical estrogen therapy (P < 0.001) and laser therapy (P < 0.001) groups. Subjective evaluation through physical examination showed a significant improvement in atrophy in both the groups. Conclusion: Despite the nonequivalence with topical estrogen therapy, our data suggest that laser therapy is an effective method for the treatment of vulvovaginal atrophy.

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CD4+CD8+ thymocytes and thymic stroma cells express ERalpha and ERbeta. In vivo and in vitro we showed that estrogen treatment increases FasL expression while decreasing thymus cell number. These findings support the hypothesis that estrogen-induced thymic atrophy occurs as a result of apoptosis and is mediated by estrogen-induced FasL expression.