Neurodegeneration in adults as a result of alcohol abuse.
Our group studies the molecular and cellular effects of ethanol in the adult and developing brain. We were pioneers in demonstrating that ethanol triggers neuroinflammation, brain injury, and behavioral dysfunction by interacting with TLR4, an innate glial cell membrane immune receptor.
Considering the role of extracellular vesicles (EVs) and exosomes in different neuropathological conditions, one of our current objectives is to evaluate the role of glial cell EVs in extending neuroinflammation associated with alcohol abuse. Using astrocytes in primary culture, we showed that ethanol increases the number of secreted EVs and alters their content by raising the levels of both inflammatory-related proteins (TLR4, p65, IL1R, caspase-1, and NLRP3) and miRNAs (mir-146, mir-182, and mir-200b). However, no changes were observed in EVs from ethanol-treated astrocytes in which TLR4 had been knocked out.
Notably, when cultured cortical neurons were incubated with ethanol-treated exosomes, we observed that EVs (and their inflammation-promoting content) from astrocytes were internalized by naïve neurons, thereby triggering neuronal apoptosis. Thus, astrocyte-derived EVs may act as cellular transmitters of inflammatory signaling by spreading and amplifying the neuroinflammatory response induced by ethanol through TLR4.
Get to know us better
The people who make it all possible
Consuelo Guerri Sirera
Susana Mellado Valero
Carlos Manuel Cuesta Díaz
Our scientific contributions
TLR4 participates in the transmission of ethanol-induced neuroinflammation via astrocyte-derived extracellular vesicles
Ibáñez F, Montesinos J, Ureña-Peralta JR, Guerri C and Pascual M
Journal of Neuroinflammation, 2019 Jul,  DOI:  10.1186/s12974-019-1529-x,  Vol. 16,  pag. 136-136
Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation
Cantacorps L, Alfonso-Loeches S, Guerri C and Valverde O
JOURNAL OF PSYCHOPHARMACOLOGY, 2019 Dec,  DOI:  10.1177/0269881119856001,  Vol. 33,  pag. 1562-1572
Impact of neuroimmune activation induced by alcohol or drug abuse on adolescent brain development
Guerri C and Pascual M
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2019 Oct,  DOI:  10.1016/j.ijdevneu.2018.11.006,  Vol. 77,  pag. 89-98
Gender differences in the inflammatory cytokine and chemokine profiles induced by binge ethanol drinking in adolescence
M. PASCUAL, J. MONTESINOS, M. MARCOS, J. TORRES, P. COSTA-ALBA, F. GARCIA-GARCIA, F. LASO and C. GUERRI
ADDICTION BIOLOGY, 2017 Nov,  DOI:  10.1111/adb.12461,  Vol. 22,  pag. 1829-1841
TLR4 response mediates ethanol-induced neurodevelopment alterations in a model of fetal alcohol spectrum disorders
M. PASCUAL, J. MONTESINOS, S. MONTAGUD-ROMERO, J. FORTEZA, M. RODRIGUEZ-ARIAS, J. MINARRO and C. GUERRI
Journal of Neuroinflammation, 2017 Jul,  DOI:  10.1186/s12974-017-0918-2,  Vol. 14,  pag. 145-145