Social isolation disrupts hippocampal neurogenesis in young non-human primates

Social relationships are crucial for the development and maintenance of normal behavior in non-human primates. Animals that are raised in isolation develop abnormal patterns of behavior that persist even when they are later reunited with their parents. in rodents, social isolation is a stressful event and is associated with a decrease in hippocampal neurogenesis but considerably less is known about the effects of social isolation in non-human primates during the transition from adolescence to adulthood. To investigate how social isolation affects young marmosets, these were isolated from other members of the colony for 1 or 3 weeks and evaluated for alterations in their behavior and hippocampal cell proliferation. We found that anxiety-related behaviors like scent-marking and locomotor activity increased after social isolation when compared to baseline levels. in agreement, grooming an indicative of attenuation of tension was reduced among isolated marmosets. These results were consistent with increased cortisol levels after 1 and 3 weeks of isolation. After social isolation (1 or 3 weeks), reduced proliferation of neural cells in the subgranular zone of dentate granule cell layer was identified and a smaller proportion of BrdU-positive cells underwent neuronal fate (doublecortin labeling). Our data is consistent with the notion that social deprivation during the transition from adolescence to adulthood leads to stress and produces anxiety-like behaviors that in turn might affect neurogenesis and contribute to the deleterious consequences of prolonged stressful conditions.Universidade Federal de São Paulo, Dept Fisiol, BR-04023062 São Paulo, BrazilUniv Fed Rio Grande do Norte, Dept Fisiol, BR-59072970 Natal, RN, BrazilUniv Fed Rural Rio de Janeiro, Dept Ciencias Fisiol, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Fisiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Long-lasting anxiolytic effect of neural precursor cells freshly prepared but not neurosphere-derived cell transplantation in newborn rats

Background: the GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have been reported for obtaining MGE precursor cells for transplantation: fresh and neurosphere dissociated cells. Here, we investigated the effects generated by transplantation of the two types of cell preparations on anxiety behavior in rats.Results: We transplanted freshly dissociated or neurosphere dissociated cells into the neonate brain of male rats on postnatal (PN) day 2-3. At early adulthood (PN 62-63), transplanted animals were tested in the Elevated Plus Maze (EPM). To verify the differentiation and migration pattern of the transplanted cells in vitro and in vivo, we performed immunohistochemistry for GFP and several interneuron-specific markers: neuropeptide Y (NPY), parvalbumin (PV) and calretinin (CR). Cells from both types of preparations expressed these interneuronal markers. However, an anxiolytic effect on behavior in the EPM was observed in animals that received the MGE-derived freshly dissociated cells but not in those that received the neurosphere dissociated cells.Conclusion: Our results suggest a long-lasting anxiolytic effect of transplanted freshly dissociated cells that reinforces the inhibitory function of the GABAergic neuronal circuitry in the hippocampus related to anxiety-like behavior in rats.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Fisiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUNIFESP, Dept Biociencias, BR-11015020 Santos, SP, BrazilUniv Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, BR-90035003 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Fisiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUNIFESP, Dept Biociencias, BR-11015020 Santos, SP, BrazilWeb of Scienc

Comparative assessment of stem cell therapy in a rat model of amyotrophic lateral sclerosis

BV UNIFESP: Teses e dissertaçõe

Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to immunomodulation. To this end, Wistar rats (200-250 g) were submitted to 1-hour ischemia and treated with NPCs (4 x 10(6) cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with carboxyfluorescein diacetate succinimydylester (CFSE). Kidneys were harvested for analysis of cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78mg/dl, p < 0.05) and acute tubular necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-CFSE and glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker) mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-beta and TNF-alpha expression and higher anti-inflammatory IL-4 and IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory cytokines (IL-1 beta, TNF-alpha and INF-gamma). Our data suggested that NPC therapy improved renal function by influencing immunological responses. Copyright (C) 2009 S. Karger AG, BaselMCT/CT-Saude/Decit/SCTIE/MSFundacao de Apoio a Pesquisa do Estado de São PauloUniv São Paulo, Dept Immunol, Inst Biomed Sci, Lab Transplantat Immunobiol, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Lab Imunol Clin & Expt, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Neurophysiol Lab, Div Physiol, São Paulo, BrazilUniv Estadual Campinas, Div Nephrol, Campinas, SP, BrazilUniv Fed Triangulo Mineiro, Div Pathol, Belo Horizonte, MG, BrazilInst Israelita Ensino & Pesquisa Albert Einstein, São Paulo, BrazilUniversidade Federal de São Paulo, Lab Imunol Clin & Expt, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Neurophysiol Lab, Div Physiol, São Paulo, BrazilMCT/CT-Saude/Decit/SCTIE/MS: 552307/2005-0Fundacao de Apoio a Pesquisa do Estado de São Paulo: 04/08311-6Fundacao de Apoio a Pesquisa do Estado de São Paulo: 04/13826-5Fundacao de Apoio a Pesquisa do Estado de São Paulo: 05/50085-6Fundacao de Apoio a Pesquisa do Estado de São Paulo: 07/07139-3Web of Scienc