Alzheimer's disease (AD) is the most common dementia worldwide, and is characterized by the presence, in the brain tissue, of extracellular senile plaques formed by amyloid beta (Aβ) peptide and intracellular neurofibrillary tangles of hyperphosphorylated Tau protein.These changes lead to progressive neuronal degeneration and dysfunction, resulting in severe brain atrophy and cognitive deficits. With the discovery that neurogenesis persists in the adult mammalian brain, including brain regions affected by AD, studies of the use of neural stem cells for treatment of neurodegenerative diseases in order to repair and/or prevent neuronal cell loss have increased. Here we show that leptin increases neurogenesis in the dentate gyrus of adult mice as well as in the subventricular zone both in wild type and AD transgenic mouse model. Chronic administration of leptin to young mice increased neural stem cell proliferation with significant effects on differentiation and survival of newborn cells. Expression of the long form of leptin receptor, LepRb, was detected in the neurogenic niches by reverse transcription-PCR and immunohistochemistry. Moreover, leptin modulated astrogliosis and the formation of senile plaques. Additionally, leptin led to attenuation of Aβ-induced neurodegeneration and superoxide anion production as revealed by Fluoro-Jade B and dihydroethidium (DHE) staining. Our study contributes to the understanding of the effects of leptin in the brain that may lead to the development of new therapies to treat Alzheimer's disease.

Objective: to determine the immunoexpression of cytochrome P-450 (CYP19), an enzyme associated with the conversion of androstenedione to estradiol in the ovaries of pinealectomized female rats after melatonin treatment. Methods: Thirty female rats (Rattus norvegicus albinus), adult, virgin from Universidade de São Paulo-Escola Paulista de Medicina (UNIFESP/EPM) biotery were separated in three groups of 10 animals each: GI-Sham (falsely pinealectomized) received vehicle; GIIpinealectomized who received vehicle; GIII-pinealectomized with melatonin reposition (10μg/night, each animal) for 60 consecutive days (Fig. 1 and 2). After this period, animals were anesthetized and ovaries were collected, fixed in 10% buffered formaldehyde and processed for paraffin embedding. From the paraffin blocks, 5μm thick sections were collected to silanized slides and submitted to immunohistochemistry for CYP19 detection. Images were obtained using a light microscope (Axiolab Standard 2.0-Carl Zeiss) attached to a high definition camera (AxioCam MRC-Carl Zeiss) and by the image analyzing image (AxioVision Rel. 4.8.2-Carl Zeiss). Reaction expression was analyzed and quantified according with the color intensity with the aid of the Image J Pro Plus, having photographed 5 fields each slide, with the 40× objective. Obtained data was submitted to statistical analysis using ANOVA test complemented by the Tukey-Kramer test (p<0,05). Results: Histological sections underwent immunostaining CPY19 showed that the expression of CPY19 was higher in pinealectomized (GII = 84.43 ± 5.90 *) compared to Sham groups (GI = 64.71 ± 4.06) and pinealectomized treated with melatonin (GIII = 58.35 ± 8.90) (* p <0.05)(Fig. 3) Conclusions: Our results showed that melatonin affects ovarian steroidogenesis in female rats. [2]