eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom

Soares, Edilene Siqueira; Mendonça, Monique Culturato Padilha; Cruz‐Höfling, Maria Alice da

doi:10.1016/j.toxicon.2015.07.009

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…PNV also activates neurons, and induces expression of GFAP, S100 and pro-inflammatory cytokines in astrocytes of the cerebellum and hippocampus with evidences of nitric oxide (NO) derived from neuronal and endothelial nitric oxide synthase (nNOS, eNOS, respectively) mediation [33,34,35]. …”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the rise in the expression of Cav-1 (WB and IHC data) promoted by PNV suggests eNOS inhibition and poor availability of oxide nitric (NO) and thus endothelium dysfunction. Recent study of our group has shown that PNV proper reduces availability of NO by leading to eNOS uncoupling [35]; at early periods following envenomation when toxic manifestation is severe, there is monomerization of eNOS and incapacity of the enzyme to produce NO, leading to superoxide production and endothelial/vascular BBB dysfunction [54]. …”

Section: Discussionmentioning

confidence: 99%

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Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Soares

Stávale

Mendonça

et al. 2016

IJMS

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We have previously demonstrated that Phoneutria nigriventer venom (PNV) causes blood–brain barrier (BBB) breakdown, swelling of astrocytes end-feet and fluid permeation into brain interstitium in rats. Caveolae and water channels respond to BBB alterations by co-participation in shear stress response and edema formation/resolution. Herein, we showed post-natal developmental-related changes of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1), the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4 (AQP4), the main water channel protein expressed in astrocytic peri-vascular end-feet processes, in the hippocampus of rats intraperitoneally-administered PNV. Western blotting protein levels; immunohistochemistry (IHC) protein distribution in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain Reaction (qPCR) were assessed in post-natal Day 14 (P14) and 8–10-week-old rats over critical periods of envenomation. The intensity and duration of the toxic manifestations indicate P14 neonate rats more vulnerable to PNV than adults. Histologically, the capillaries of P14 and 8–10-week-old rats treated with PNV showed perivascular edema, while controls did not. The intensity of the toxic manifestations in P14 decreases temporally (2 > 5 > 24 h), while inversely the expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1 showed the least expression at 2 h when toxic manifestation was maximal. Subfield IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic manifestations were absent, whereas in 8–10-week-old rats Cav-1 peaked at 2 h when toxic signs were highest, and progressively attenuated such increases until 24 h, remaining though significantly above baseline. Considering astrocyte-endothelial physical and functional interactions, we hypothesize that age-related modulations of AQP4 and Cav-1 might be linked both to changes in functional properties of astrocytes during post-natal development and in the BBB breakdown induced by the venom of P. nigriventer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Soares

Stávale

Mendonça

et al. 2016

IJMS

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“…Some cases of phoneutrism can evolve to death. 1,3,6,7 Spiders of the genus Latrodectus (Walcknaer, 1805) (Aranae: Theridiidae) have a worldwide distribution occurring on many continents and islands. The genus Latrodectus contains about 31 species of spiders identified, which are commonly known as black widows.…”

Section: Methodsmentioning

confidence: 99%

Arthropods of medical importance and profile of associated accidents for the municipality of São Miguel do Oeste, Santa Catarina state

Cozzer

Morsbacher

Bortolanza

et al. 2019

Rev Epidemiol Control Infect

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Justificativa e Objetivos: Artrópodes são de longe os animais mais comuns na Terra em indivíduos totais e táxons descritos. No Brasil, a importância dos acidentes por animais peçonhentos, nos quais se incluem acidentes por artrópodes peçonhentos, pode ser expressa pelos mais de 100 mil casos e cerca de 200 óbitos registrados ao ano. Os serviços públicos de saúde têm aumentado as notificações deste tipo de acidente nos estados da região sul do Brasil, principalmente os ocorridos na zona rural. Este acréscimo decorre das modificações do ambiente natural pelo desmatamento e pelos diferentes usos do solo pelo homem. O objetivo deste estudo foi descrever a ocorrência de acidentes com artrópodes peçonhentos e o perfil social dos acidentes associados no município de São Miguel do Oeste, no período de 2007 a 2016. Métodos: Trata-se de um transversal e retrospectivo, com dados obtidos nas fichas de notificação e investigação individual do Sistema de Informação de Agravos de Notificação (Sinan). Resultados: A predominância dos acidentes envolveu pessoas do sexo masculino para lonomismo e outras lagartas venenosas e do sexo feminino para loxoscelismo, ocorreram mais frequentemente no ambiente urbano e envolveram a faixa etária entre 20 a 59 anos, afetando a população economicamente ativa. Conclusões: O estudo contribui para a compreensão dos determinantes para a ocorrência de animais peçonhentos em uma região de fronteira e fornece embasamento para as políticas públicas de promoção da saúde e de prevenção de agravos. PALAVRAS-CHAVE: Animais venenosos. Promoção de saúde. Saúde pública.

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“…Nevertheless, it was suggested that eNOS-derived NO is a neuromodulator that participates in the BBB-mediated control of the cerebellum in experimental models [36].…”

Section: •−mentioning

confidence: 99%

“…Therefore, the NO produced by NOS results in vasodilation and controls vascular resistance, platelet adhesion and aggregation, leukocyte-to-endothelium interaction, and the maintenance of BBB integrity [36].…”

Section: •−mentioning

confidence: 99%

Role of Nitric Oxide Synthase in the Function of the Central Nervous System under Normal and Infectious Conditions

Reis¹,

Gonçalves-de-Albuquerque²,

Maron‐Gutierrez³

et al. 2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide (NO) was discovered as an endothelium-derived relaxing factor more than two decades ago. Since then, it has been shown to participate in many pathways. NO has been described as a key mediator of different pathways in the central nervous system (CNS) in both healthy and diseased processes. The three isoforms of nitric oxide synthase differ in their activity patterns and expression in different cells. Neuronal nitric oxide synthase (nNOS) is localized in synaptic spines, astrocytes, and the loose connective tissue surrounding blood vessels in the brain; eNOS is present in both cerebral vascular endothelial cells and motor neurons; and iNOS is induced in astrocytes and microglia under pathological conditions. During physiological processes, NO produced by eNOS/nNOS, respectively, controls blood flow activation, and act as a messenger during long-term potentiation (LTP). However, under pathological conditions, eNOS appears to be impaired, leading to a reduction in blood flow and, consequently, low oxygen/metabolites delivery, efflux of toxicological agents from the brain tissue and disturbance in the blood-brain barrier. The NO produced by iNOS in glial cells and nNOS, which triggers the NMDA-excitotoxic pathway, combines with superoxide anion and results in peroxynitrite synthesis, a potent free radical that contributes to tissue damage in the brain. Here, we intend to show the controversial role of the nitric oxide delivered by the three isoforms of the nitric oxide synthase in the CNS, assess its impact under healthy/pathological conditions and speculate on its possible sequela, particularly in long-term cognitive decline.

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eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom

Cited by 12 publications

References 47 publications

Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the Toxic Effect of Phoneutria nigriventer Spider Venom

Arthropods of medical importance and profile of associated accidents for the municipality of São Miguel do Oeste, Santa Catarina state

Role of Nitric Oxide Synthase in the Function of the Central Nervous System under Normal and Infectious Conditions

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