Nitric Oxide Regulates Neurogenesis in the Hippocampus following Seizures

Hippocampal neurogenesis is changed by brain injury. When neuroinflammation accompanies injury, activation of resident microglial cells promotes the release of inflammatory cytokines and reactive oxygen/nitrogen species like nitric oxide (NO). In these conditions, NO promotes proliferation of neural stem cells (NSC) in the hippocampus. However, little is known about the role of NO in the survival and differentiation of newborn cells in the injured dentate gyrus. Here we investigated the role of NO following seizures in the regulation of proliferation, migration, differentiation, and survival of NSC in the hippocampus using the kainic acid (KA) induced seizuremouse model. We show that NO increased the proliferation of NSC and the number of neuroblasts following seizures but was detrimental to the survival of newborn neurons. NO was also required for the maintenance of long-term neuroinflammation. Taken together, our data show that NO positively contributes to the initial stages of neurogenesis following seizures but compromises survival of newborn neurons.Foundation for Science and Technology (FCT, Portugal); COMPETE; FEDER [PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012, PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014]; FCT, Portugal [SFRH/BPD/78901/2011, SFRH/BD/77903/2011

Regulation of injury-induced neurogenesis by Nitric Oxide

The finding that neural stem cells (NSCs) are able to divide, migrate, and differentiate into several cellular types in the adult brain raised a new hope for restorative neurology. Nitric oxide (NO), a pleiotropic signaling molecule in the central nervous system (CNS), has been described to be able to modulate neurogenesis, acting as a pro-or antineurogenic agent. Some authors suggest that NO is a physiological inhibitor of neurogenesis, while others described NO to favor neurogenesis, particularly under inflammatory conditions. Thus, targeting the NO system may be a powerful strategy to control the formation of new neurons. However, the exact mechanisms by which NO regulates neural proliferation and differentiation are not yet completely clarified. In this paper we will discuss the potential interest of the modulation of the NO system for the treatment of neurodegenerative diseases or other pathological conditions that may affect the CNS.Foundation for Science and Technology, (FCT, Portugal); COMPETE

Differential contribution of the guanylyl cyclase-cyclic GMP-protein kinase g pathway to the proliferation of neural stem cells stimulated by nitric oxide

Nitric oxide (NO) is an important inflammatory mediator involved in the initial boost in the proliferation of neural stem cells following brain injury. However, the mechanisms underlying the proliferative effect of NO are still unclear. The aim of this work was to investigate whether cyclic GMP (cGMP) and the cGMP-dependent kinase (PKG) are involved in the proliferative effect triggered by NO in neural stem cells. For this purpose, cultures of neural stem cells isolated from the mouse subventricular zone (SVZ) were used. We observed that long-term exposure to the NO donor (24 h), NOC-18, increased the proliferation of SVZ cells in a cGMP-dependent manner, since the guanylate cyclase inhibitor, ODQ, prevented cell proliferation. Similarly to NOC-18, the cGMP analogue, 8-Br-cGMP, also increased cell proliferation. Interestingly, shorter exposures to NO (6 h) increased cell proliferation in a cGMP-independent manner via the ERK/MAP kinase pathway. The selective inhibitor of PKG, KT5823, prevented the proliferative effect induced by NO at 24 h but not at 6 h. In conclusion, the proliferative effect of NO is initially mediated by the ERK/MAPK pathway, and at later stages by the GC/cGMP/PKG pathway. Thus, our work shows that NO induces neural stem cell proliferation by targeting these two pathways in a biphasic manner. Copyright (C) 2012 S. Karger AG, BaselCalouste Gulbenkian Foundation; L'Oreal; UNESCO; Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/78901/2011, SFRH/BD/23754/2005, SFRH/BD/38127/2007]; COMPETE; FEDER [PTDC/SAU-NEU/102612/2008]info:eu-repo/semantics/publishedVersio

Where to "Rock"? Choice of retreat sites by a gecko in a semi-arid habitat

The Selvagens gecko (Tarentola boettgeri bischoffi Joger, 1984) is a medium sized gecko endemic to the Selvagens archipelago, Madeira, Portugal. The biology of this gecko is poorly known and in this study we present the first evidence regarding its habitat use. In 2010 (spring and autumn) and 2011 (spring), we collected data on the characteristics of the habitat surrounding 168 rocks used by these geckos as retreat sites, as well as on 75 randomly selected rocks. We also recorded body measurements of the individuals caught under each rock. In both seasons retreat site occupancy was found to be related to rock area, with geckos being found mainly under large rocks. Interestingly, we found that in spring heavier males, in better body condition, occupied the largest rocks and larger geckos occupied rocks closer to creek beds. Our results shed some light upon the behavioural ecology of this nocturnally active ecto-therm, that spends the day under a retreat site: i) intraspecific competition may be an ecological factor prevalent in this species, since larger individuals occupy larger rocks, located in a presumably high quality micro-habitat; ii) the possibility of spring territoriality in males, that compete for good quality shelters.Peer reviewe

Where to “Rock”? Choice of retreat sites by a gecko in a semi-arid habitat

The Selvagens gecko (Tarentola boettgeri bischoffi Joger, 1984) is a medium sized gecko endemic to the Selvagens archipelago, Madeira, Portugal. The biology of this gecko is poorly known and in this study we present the first evidence regarding its habitat use. In 2010 (spring and autumn) and 2011 (spring), we collected data on the characteristics of the habitat surrounding 168 rocks used by these geckos as retreat sites, as well as on 75 randomly selected rocks. We also recorded body measurements of the individuals caught under each rock. In both seasons retreat site occupancy was found to be related to rock area, with geckos being found mainly under large rocks. Interestingly, we found that in spring heavier males, in better body condition, occupied the largest rocks and larger geckos occupied rocks closer to creek beds. Our results shed some light upon the behavioural ecology of this nocturnally active ectotherm, that spends the day under a retreat site: i) intraspecific competition may be an ecological factor prevalent in this species, since larger individuals occupy larger rocks, located in a presumably high quality micro-habitat; ii) the possibility of spring territoriality in males, that compete for good quality shelters

Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling

Neuroinflammation is characterized by activation of microglial cells, followed by production of nitric oxide (NO), which may have different outcomes on neurogenesis, favoring or inhibiting this process. In the present study, we investigated how the inflammatory mediator NO can affect proliferation of neural stem cells (NSCs), and explored possible mechanisms underlying this effect. We investigated which mechanisms are involved in the regulation of NSC proliferation following treatment with an inflammatory stimulus (lipopolysaccharide plus IFN-gamma), using a culture system of subventricular zone (SVZ)-derived NSCs mixed with microglia cells obtained from wild-type mice (iNOS(+/+)) or from iNOS knockout mice (iNOS(-/-)). We found an impairment of NSC cell proliferation in iNOS(+/+) mixed cultures, which was not observed in iNOS(-/-) mixed cultures. Furthermore, the increased release of NO by activated iNOS(+/+) microglial cells decreased the activation of the ERK/MAPK signaling pathway, which was concomitant with an enhanced nitration of the EGF receptor. Preventing nitrogen reactive species formation with MnTBAP, a scavenger of peroxynitrite (ONOO-), or using the ONOO- degradation catalyst FeTMPyP cell proliferation and ERK signaling were restored to basal levels in iNOS(+/+) mixed cultures. Moreover, exposure to the NO donor NOC-18 (100 mu M), for 48 h, inhibited SVZ-derived NSC proliferation. Regarding the antiproliferative effect of NO, we found that NOC-18 caused the impairment of signaling through the ERK/MAPK pathway, which may be related to increased nitration of the EGF receptor in NSC. Using MnTBAP nitration was prevented, maintaining ERK signaling, rescuing NSC proliferation. We show that NO from inflammatory origin leads to a decreased function of the EGF receptor, which compromised proliferation of NSC. We also demonstrated that NO-mediated nitration of the EGF receptor caused a decrease in its phosphorylation, thus preventing regular proliferation signaling through the ERK/MAPK pathway.Foundation for Science and Technology, (FCT, Portugal); COMPETE; FEDER [PEst-C/SAU/LA0001/2013-2014, PEst-OE/EQB/LA0023/2013-2014, PTDC/SAU-NEU/102612/2008, PTDC/NEU-OSD/0473/2012]; FCT, Portugal [SERH/BPD/78901/2011, SERH/BD/38127/2007, SFRH/BD/77903/2011, SFRH/BD/79308/2011]info:eu-repo/semantics/publishedVersio

Valuable Secondary Habitats or Hazardous Ecological Traps? Environmental Risk Assessment of Minor and Trace Elements in Fly Ash Deposits across the Czech Republic

Deposits of coal combustion wastes, especially fly ash, are sources of environmental and health risks in industrial regions. Recently, fly ash deposits have been reported as habitat surrogates for some threatened arthropods in Central Europe. However, the potential environmental risks of fly ash have not yet been assessed in the region. We analysed concentrations of 19 minor and trace elements in 19 lignite combustion waste deposits in the Czech Republic. We assessed their environmental risks by comparison with the national and EU legislation limits, and with several commonly used indices. Over 50% of the samples exceeded the Czech national limits for As, Cu, V, or Zn, whilst only V exceeded the EU limits. For some studied elements, the high-risk indices were detected in several localities. Nevertheless, the measured water characteristics, the long-term presence of fly ash, previous leaching by acid rains, and the low amount of organic matter altogether can infer low biological availability of these elements. We presume the revealed high concentrations of some heavy metals at some studied sites can be harmful for some colonising species. Nevertheless, more ecotoxicological research on particular species is needed for final decision on their conservation potential for terrestrial and freshwater biota.info:eu-repo/semantics/publishedVersio

Reflexo: Ferramenta Pedagógica para uma nova relação entre a escola e as comuniddaes ciganas

Os estereótipos, e consequente discriminação da comunidade cigana, são uma realidade que se mantém nos dias de hoje. Os obstáculos observados ao longo do processo de integração desta comunidade na cultura maioritária refletem-se particularmente no elevado abandono e insucesso escolares. Foi com base na constatação destes problemas que surgiu o Projeto Reflexo - Imagens Positivas que, numa perspetiva de educação intercultural, tem como objetivo colocar a comunidade cigana e não cigana a refletir sobre os seus valores e tradições, no sentido de potenciar o diálogo e um maior conhecimento e aceitação mútuos. Pretende-se, deste modo, através de uma escola mais inclusiva, empoderar jovens da comunidade cigana, levando a que reflitam sobre o que é valioso na sua cultura e de que forma se podem inserir na cultura maioritária sem perder a sua matriz própria. A escola aparece assim como instrumento de uma política emancipadora e espaço da educação política das novas gerações, procurando através da diferenciação e do multiculturalismo curricular promover uma maior justiça e equidade. Em suma, através da conceção, experimentação e edição de um recurso com atividades pedagógicas a ser utilizado nas escolas e envolvendo ativamente, neste processo, alunos e alunas, professores e professoras e ainda encarregados e encarregadas de educação, pretende-se contribuir para: – a permanência das crianças ciganas na Escola para além do 1º e 2º ciclos do Ensino Básico, combatendo, assim, o abandono escolar nesta população; – o respeito de toda a Escola em relação à comunidade cigana, através da valorização das diferenças culturais e promoção de uma cultura de não discriminação no contexto escolar (ou seja, uma Escola inclusiva).Edição financiada pelo FAPE - Fundo de Apoio à Estratégia Nacional para a Integração das Comunidades Ciganas (ENICC) promovido pelo Alto Comissariado para as Migrações I.P (ACM I.P).info:eu-repo/semantics/publishedVersio