| Autor: |
Gustavo Gastão Davanzo, Gisele Castro, Lauar de Brito Monteiro, Bianca Gazieri Castelucci, Vitor Hugo Jaccomo, Felipe Corrêa da Silva, Ana Maria Marques, Carolina Francelin, Bruna Bueno de Campos, Cristhiane Fávero de Aguiar, Paulo Pinto Joazeiro, Sílvio Roberto Consonni, Alessandro dos Santos Farias, Pedro M. Moraes-Vieira |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Multiple Sclerosis and Related Disorders. 72:104605 |
| ISSN: |
2211-0348 |
| DOI: |
10.1016/j.msard.2023.104605 |
| Popis: |
Obesity-induced insulin resistance (OIR) has been associated with an increased prevalence of neurodegenerative disorders such as multiple sclerosis. Obesity results in increased blood-brain barrier (BBB) permeability, specifically in the hypothalamic regions associated with the control of caloric intake. In obesity, the chronic state of low-grade inflammation has been implicated in several chronic autoimmune inflammatory disorders. However, the mechanisms that connect the inflammatory profile of obesity with the severity of experimental autoimmune encephalomyelitis (EAE) are poorly defined. In this study, we show that obese mice are more susceptible to EAE, presenting a worse clinical score with more severe pathological changes in the spinal cord when compared with control mice. Analysis of immune infiltrates at the peak of the disease shows that high-fat diet (HFD)- and control (chow)-fed groups do not present any difference in innate or adaptive immune cell compartments, indicating the increased severity occurs prior to disease onset. In the setting of worsening EAE in HFD-fed mice, we observed spinal cord lesions in myelinated regions and (blood brain barrier) BBB disruption. We also found higher levels of pro-inflammatory monocytes, macrophages, and IFN-γ+CD4+ T cells in the HFD-fed group compared to chow-fed animals. Altogether, our results indicate that OIR promotes BBB disruption, allowing the infiltration of monocytes/macrophages and activation of resident microglia, ultimately promoting CNS inflammation and exacerbation of EAE. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect