Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/199925
Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
An in‐depth understanding of the neurodegenerative component of multiple sclerosis (MS) is crucial for the design of therapeutic approaches that may stop disease progression. Astrocytes have emerged as key contributors to the pathogenesis of MS. 1 However, the mechanisms underlying the regulation of maladaptive astrocytic responses remain unknown. In this report, we show that a high inflammatory activity in MS patients at disease onset induces a specific reactive astrocyte state that triggers synaptopathy and contributes to neuronal damage in vitro and ex vivo suggesting potential mechanisms that may ultimately lead to neurodegeneration. To investigate whether astrocytes are essential contributors to neuronal damage in MS, we cultured purified astrocytes with cerebrospinal fluid (CSF) samples from MS patients with high inflammatory activity at disease onset (MS‐High, Table S1). Then, we examined the effect of astrocytic secretomes on neurons (Figure 1A). Astrocytes became reactive upon high inflammatory CSF exposure (Figure 1B) and induced morphological alterations typically observed in neurodegenerative disorders, such as a less complex dendritic tree due to decreased arborisation (Figure 1C, D). Moreover, these abnormalities were accompanied with synaptic plasticity impairment (Figure 1E, F). Considering that a high lesion load at disease onset has been associated with an increased risk of neurological disability development, 2 we assessed whether the non‐cell‐autonomous effect on neuronal plasticity could be influenced by the degree of inflammatory activity of MS patients (Figure 2A and Table S1). Interestingly, we observed a direct correlation between the degree of inflammatory exposure and the extent of both astrocyte‐mediated synaptopathy (Figure 2B, C) and dendrite arborisation impairment.
Matèries (anglès)
Citació
Citació
MATUTE BLANCH, Clara, BRITO, Verónica, MIDAGLIA, Luciana, VILLAR, Luisa m., GARCÍA-DÍAZ BARRIGA, Gerardo, GUZMÁN DE LA FUENTE, Alerie, BORRÀS, Eva, FERNÁNDEZ, Sara (fernández garcía), CALVO BARREIRO, Laura, MIGUEZ, Andrés, COSTA FROSSARD, Lucienne, PINTEAC, Rucsanda, SABIDÓ AGUADÉ, Eduard, ALBERCH I VIÉ, Jordi, FITZGERALD, Denise c., MONTALBÁN GAIRÍN, Xavier, COMABELLA, Manuel. Inflammation in multiple sclerosis induces a specific reactive astrocyte state driving non-cell-autonomous neuronal damage. _Clinical and Translational Medicine_. 2022. Vol. 12, núm. 5. [consulta: 23 de gener de 2026]. ISSN: 2001-1326. [Disponible a: https://hdl.handle.net/2445/199925]