| Author | Obadia, Nathalie | |
| Author | Andrade, Giulia | |
| Author | Leardini-Tristão, Marina | |
| Author | Albuquerque, Letícia | |
| Author | Garcia, Celina | |
| Author | Lima, Flavia | |
| Author | Daleprane, Júlio | |
| Author | Faria Neto, Hugo C. Castro | |
| Author | Tibiriçá, Eduardo | |
| Author | Estato, Vanessa | |
| Access date | 2022-06-14T13:02:44Z | |
| Available date | 2022-06-14T13:02:44Z | |
| Document date | 2022 | |
| Citation | OBADIA, Nathalie et al. TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice. Journal of Neuroinflammation, v. 19, 104, p. 1 - 18, 2022. | pt_BR |
| ISSN | 1742-2084 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/53249 | |
| Language | eng | pt_BR |
| Publisher | BMC | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Microcirculação cerebral | pt_BR |
| Subject in Portuguese | Consumo de dieta rica em gordura | pt_BR |
| Subject in Portuguese | TLR4 | pt_BR |
| Subject in Portuguese | Neuroinflamação | pt_BR |
| Subject in Portuguese | Células da glia | pt_BR |
| Title | TLR4 mutation protects neurovascular function and cognitive decline in high‑fat diet‑fed mice | pt_BR |
| Type | Article | |
| DOI | 10.1186/s12974-022-02465-3 | |
| Abstract | Background: Metabolic syndrome (MS) is defined as a low-grade proinflammatory state in which abnormal metabolic
and cardiovascular factors increase the risk of developing cardiovascular disease and neuroinflammation. Events,
such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia,
and sympathetic hyperactivity in MS may contribute to the direct or indirect activation of Toll-like receptors (TLRs),
specifically TLR4, which is thought to be a major component of this syndrome. Activation of the innate immune
response via TLR4 may contribute to this state of chronic inflammation and may be related to the neuroinflammation
and neurodegeneration observed in MS. In this study, we investigated the role of TLR4 in the brain microcirculation
and in the cognitive performance of high-fat diet (HFD)-induced MS mice.
Methods: Wild-type (C3H/He) and TLR4 mutant (C3H/HeJ) mice were maintained under a normal diet (ND) or a HFD
for 24 weeks. Intravital video-microscopy was used to investigate the functional capillary density, endothelial function,
and endothelial–leukocyte interactions in the brain microcirculation. Plasma concentrations of monocyte chemoattractant
protein-1 (MCP-1), adipokines and metabolic hormones were measured with a multiplex immunoassay. Brain
postsynaptic density protein-95 and synaptophysin were evaluated by western blotting; astrocytic coverage of the
vessels, microglial activation and structural capillary density were evaluated by immunohistochemistry.
Results: The HFD-induced MS model leads to metabolic, hemodynamic, and microcirculatory alterations, as evidenced
by capillary rarefaction, increased rolling and leukocyte adhesion in postcapillary venules, endothelial
dysfunction, and less coverage of astrocytes in the vessels, which are directly related to cognitive decline and neuroinflammation.
The same model of MS reproduced in mice deficient for TLR4 because of a genetic mutation does not
generate such changes. Furthermore, the comparison of wild-type mice fed a HFD and a normolipid diet revealed
differences in inflammation in the cerebral microcirculation, possibly related to lower TLR4 activation.
Conclusions: Our results demonstrate that TLR4 is involved in the microvascular dysfunction and neuroinflammation
associated with HFD-induced MS and possibly has a causal role in the development of cognitive decline. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Glial Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Laboratório de Glial Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade do Estado do Rio de Janeiro. Laboratório Interdisciplinar de Avaliação Nutricional. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Nacional de Cardiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Brain microcirculation | pt_BR |
| Subject | High-fat diet consumption | pt_BR |
| Subject | TLR4 | pt_BR |
| Subject | Neuroinflammation | pt_BR |
| Subject | Glial cells | pt_BR |
