Sevillano Fernández, JulioRodríguez Zapata, MaríaRamos Álvarez, María del PilarRamos González, Ana MaríaVicente Rodríguez, MartaPascual-Teresa Fernández, Beatriz deZapico Rodríguez, José MaríaFontán Baselga, TeresaCarrasco, JavierGalán Llario, Milagros MaríaMoreno Herradón, MarcoDe Pascual Teresa, BeatrizGramage, EstherHerradón Gil-Gallardo, GonzaloOvejero Benito, María del CarmenPérez García, CarmenUniversidad San Pablo-CEU. Facultad de FarmaciaUniversidad San Pablo-CEU. Instituto de Estudios de las Adicciones (IEA-CEU)2023-07-152023-07-152023-01-26Milagros Galán-Llario, María Rodríguez-Zapata, Esther Gramage, Marta Vicente-Rodríguez, Teresa Fontán-Baselga, María Carmen Ovejero-Benito, Carmen Pérez-García, Javier Carrasco, Marco Moreno-Herradón, Julio Sevillano, María Pilar Ramos-Álvarez, José María Zapico, Beatriz de Pascual-Teresa, Ana Ramos, Gonzalo Herradón, Receptor protein tyrosine phosphatase β/ζ regulates loss of neurogenesis in the mouse hippocampus following adolescent acute ethanol exposure, NeuroToxicology, Volume 94, 2023, Pages 98-107, ISSN 0161-813X, https://doi.org/10.1016/j.neuro.2022.11.008.http://hdl.handle.net/10637/14550Adolescence is a critical period for brain maturation in which this organ is more vulnerable to the damaging effects of ethanol. Administration of ethanol in mice induces a rapid cerebral upregulation of pleiotrophin (PTN), a cytokine that regulates the neuroinflammatory processes induced by different insults and the behavioral effects of ethanol. PTN binds Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ and inhibits its phosphatase activity, suggesting that RPTPβ/ζ may be involved in the regulation of ethanol effects. To test this hypothesis, we have treated adolescent mice with the RPTPβ/ζ inhibitor MY10 (60 mg/kg) before an acute ethanol (6 g/kg) administration. Treatment with MY10 completely prevented the ethanol-induced neurogenic loss in the hippocampus of both male and female mice. In flow cytometry studies, ethanol tended to increase the number of NeuN+/activated Caspase-3+ cells particularly in female mice, but no significant effects were found. Ethanol increased Iba1+ cell area and the total marked area in the hippocampus of female mice, suggesting sex differences in ethanol-induced microgliosis. In addition, ethanol reduced the circulating levels of IL-6 and IL-10 in both sexes, although this reduction was only found significant in males and not affected by MY10 treatment. Interestingly, MY10 alone increased the total marked area and the number of Iba1+ cells only in the female hippocampus, but tended to reduce the circulating levels of TNF-α only in male mice. In summary, the data identify a novel modulatory role of RPTPβ/ζ on ethanol-induced loss of hippocampal neurogenesis, which seems unrelated to glial and inflammatory responses. The data also suggest sex differences in RPTPβ/ζ function that may be relevant to immune responses and ethanol-induced microglial responses.application/pdfenopen accessAlcoholNeurotoxicityNeuroinflammationPleiotrophinArtículo10.1016/j.neuro.2022.11.008https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es