Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice.

Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) are involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has critical developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems, including energy homeostasis imbalance, melanocortin and reproductive system alterations and brain mass reduction in young adult mice. Since in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early life leptin deficiency in brain structure and memory function. Here, we demonstrate that leptin-deficient mice (LepOb) exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, as well as neurogenesis and memory impairments in older animals. Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signaling in adulthood.

Long-distance aberrant heterotopic connectivity in a mouse strain with a high incidence of callosal anomalies.

Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse strain as a model of CCD. We employed high-resolution anatomical MRI in 81 Balb/c and 27 C57bl6 mice to show that the Balb/c mouse strain presents a variance in the size of the CC that is 3.9 times higher than the variance of normotypical C57bl6. We also performed high-resolution diffusion-weighted imaging (DWI) in 8 Balb/c and found that the Balb/c strain shows aberrant white matter bundles, such as the Probst (5/8 animals) and the Sigmoid bundles (7/8 animals), which are similar to those found in humans with CCD. Using a histological tracer technique, we confirmed the existence of these aberrant bundles in the Balb/c strain. Interestingly, we also identified sigmoid-like fibers in the C57bl6 strain, thought to a lesser degree. Next, we used a connectome approach and found widespread brain connectivity differences between Balb/c and C57bl6 strains. The Balb/c strain also exhibited increased variability of global connectivity. These findings suggest that the Balb/c strain presents local and global changes in brain structural connectivity. This strain often presents with callosal abnormalities, along with the Probst and the Sigmoid bundles, making it is an attractive animal model for CCD and LDP in general. Our results also show that even the C57bl6 strain, which typically serves as a normotypical control animal in a myriad of studies, presents sigmoid-fashion pattern fibers laid out in the brain. These results suggest that these aberrant fiber pathways may not necessarily be a pathological hallmark, but instead an alternative roadmap for misguided axons. Such findings offer new insights for interpreting the significance of CCD-associated LDP in humans.

D2-40/podoplanin expression in chronic villitis of the placenta / Expressão de podoplanina/D2-40 em vilosite crônica placentária

ABSTRACT D2-40/podoplanin (D2-40/PDPN) is a multifunctional protein that can be expressed in lymphatic endothelium and immune cells. D2-40/ PDPN expression in chronic villitis (CV) has not been studied. In 22 cases of CV, we analyzed both D2-40/PDPN expression as well as its coexpression with immune cells markers, and the relationship with stromal cells. In the non-inflamed villi, the D2-40/PDPN positive plexiform pattern has a lymphatic-like conductive network. In the inflamed villi, the D2-40/PDPN expression, predominantly restricted to stromal cells forming a cellular network, is likely related to a phase of the inflammatory response, such as reorganization of the damaged tissue.

RESUMO Podoplanina/D2-40 (PDPN/D2-40) é uma proteína multifuncional que pode ser expressa no endotélio linfático e nas células imunes. Na vilosite crônica (VC), a expressão de PDPN/D2-40 ainda não foi estudada. Em 22 casos de VC, analisamos tanto a expressão de PDPN/D2-40 como sua coexpressão com marcadores de células imunes, além da relação com células estromais. Nas vilosidades não inflamadas, o padrão plexiforme PDPN/D2-40 positivo tem aspecto de rede condutora linfática. Nas vilosidades inflamadas, a expressão de PDPN/D2-40, com predominância restrita às células estromais, formando rede densa está, possivelmente, relacionada com uma fase da resposta inflamatória, como a reorganização do tecido danificado.

Mitomycin-treated undifferentiated embryonic stem cells as a safe and effective therapeutic strategy in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is an incurable progressive neurodegenerative disorder. Clinical presentation of PD stems largely from the loss of dopaminergic neurons in the nigrostriatal dopaminergic pathway, motivating experimental strategies of replacement based on cell therapy. Transplantation of dopaminergic neurons derived from embryonic stem cells significantly improves motor functions in rodent and non-human primate models of PD. However, protocols to generate dopaminergic neurons from embryonic stem cells generally meet with low efficacy and high risk of teratoma formation upon transplantation. To address these issues, we have pre-treated undifferentiated mouse embryonic stem cells (mESCs) with the DNA alkylating agent mitomycin C (MMC) before transplantation. MMC treatment of cultures prevented tumorigenesis in a 12 week follow-up after mESCs were injected in nude mice. In 6-OH-dopamine-lesioned mice, intrastriatal injection of MMC-treated mESCs markedly improved motor function without tumor formation for as long as 15 months. Furthermore, we show that halting mitotic activity of undifferentiated mESCs induces a four-fold increase in dopamine release following in vitro differentiation. Our findings indicate that treating mESCs with MMC prior to intrastriatal transplant is an effective to strategy that could be further investigated as a novel alternative for treatment of PD.

Avaliação microbiológica de barras de cereais diet por meio de agente ligante colágeno hidrolisado e goma acácia / Microbiological assessment of diet granola bars by hydrolyzed collagen binder and gum arabic

Objetivo: Avaliar microbiologicamente barras de cereais diet por meio litigante colágeno hidrolisado ou goma acácia. Métodos> Neste estudo fez-se o controle microbiológico (Bacillus cereus, Salmonella coliformes termotolerantes) de barras de cereais diet por meio da metodologia de superfície de resposta. Embora não seja exigido pela legislação brasileira o controle de fungos para alimentos, eles também foram investigados. Determinações de pH e de atividade da água foram realizadas devido à sua importância no desenvolvimento dos micro-organismos. Resultados: Os resultados negativos das análises microbiológicas para Bacillus cereus, Salmonellae coliformes termotolerantes mostraram que as barras de cereais analisadas atenderam às determinações legais. Possivelmente esses resultados tenham sido influenciados pelas condições de atividade da água (0,520-0,690) e de pH (4,59-5,16) das barras, desfavoráveis ao desenvolvimento dos microrganismos estudados

Determinação do índice glicêmico e da carga glicêmica de dietas hospitalares para indivíduos com diabetes. / Identification of glycemic index and glycemic load in hospital meals for individuals with diabetes.

O índice glicêmico (IG) e a carga glicêmica (CG) vêm se tornando uma nova ferramenta para auxiliar no controle da glicemia e na elaboração de dietas para pessoas com diabetes mellitus (DM). Com o objetivo de identificar a CG e o IG de dietas hospitalares oferecidas para pacientes com DM, realizou-se uma pesquisa a partir da análise das refeições oferecidas aos indivíduos com DM internados em três hospitais do município de Campinas (h1,h2,h3). O IG e a CG das dietas foram determinados, calculados e classificados de acordo com o recomendado pela literatura. Os valores de CG e IG das refeições nos três hospitais foram semelhantes e apresentaram-se, em sua maioria, inadequados. A presença de frutas, hortaliças e laticínios nas refeições influenciou o IG e a CG das dietas. O IG apresentou correlação positiva e significativa (r=0,83, p=0,04) com a CG no h2. Já no h3, o IG apresentou correlação negativa (r=0,91, p=0,02) com a CG. As dietas hospitalares apresentaram inadequados IG e CG, e a inclusão de frutas, hortaliças e alimentos lácteos pode contribuir para a diminuição do IG e CG global dessas dietas.

Glycemic index (GI) and glycemic load (GL) have become new tools for controlling glicemia and elaborating diet plans for patients with diabetes mellitus. This study aimed to identify the GI and GL of meals offered to patients with diabetes at three public hospitals (h1,h2,h3) located in Campinas, São Paulo, Brazil. The GI and GL of the meals were determined and analyzed according to literature. The mean values of GI and GL of meals were similar in all hospitals and their meals were classified as inappropriate. Fruits, vegetables and dairy products were seen to influence GI and GL of meals. GL presented a positive and significant association (r=0.83, p=0.04) with GL in h2. In h3, GI showed negative correlation (r= 0.91, p=0.02) with GL. The meals offered to patients with diabetes at the three hospitals were classified as inappropriate. The inclusion of fruits, vegetables and dairy products may contribute to a decrease of GI and GL of these meals.