Please use this identifier to cite or link to this item: http://hdl.handle.net/10637/14115

Inhibition of RPTPβ/ζ reduces chronic ethanol intake in adolescent mice and modulates ethanol effects on hippocampal neurogenesis and glial responses in a sex-dependent manner.

Title: Inhibition of RPTPβ/ζ reduces chronic ethanol intake in adolescent mice and modulates ethanol effects on hippocampal neurogenesis and glial responses in a sex-dependent manner.
Authors : Galán Llario, Milagros
Rodríguez Zapata, María
Fontán Baselga, Teresa
Gramage Caro, Esther
Vicente Rodríguez, Marta
Zapico Rodríguez, José María
De Pascual Teresa, Beatriz
Lasek, Amy W.
Herradón Gil-Gallardo, Gonzalo
Keywords: PleiotrophinPerineuronal netsPTPRZ1Neuroinflammation
Publisher: Elsevier
Citation: Milagros Galán-Llario, María Rodríguez-Zapata, Teresa Fontán-Baselga, Esther Gramage, Marta Vicente-Rodríguez, José María Zapico, Beatriz de Pascual-Teresa, Amy W. Lasek, Gonzalo Herradón, Inhibition of RPTPβ/ζ reduces chronic ethanol intake in adolescent mice and modulates ethanol effects on hippocampal neurogenesis and glial responses in a sex-dependent manner, Neuropharmacology, Volume 227, 2023, 109438, ISSN 0028-3908, https://doi.org/10.1016/j.neuropharm.2023.109438.
Abstract: Pleiotrophin (PTN) is a cytokine that modulates ethanol drinking and reward and regulates glial responses in different contexts. PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ. Inhibition of RPTPβ/ζ reduces binge-like drinking in adult male mice. Whether inhibition of RPTPβ/ζ is effective in reducing ethanol consumption during adolescence and in both sexes remained to be studied. In this work, male and female adolescent mice underwent an intermittent access to ethanol (IAE) 2-bottle choice protocol. Treatment with MY10 (60 mg/kg, i.g.), a small-molecule RPTPβ/ζ inhibitor, reduced chronic 3-week ethanol consumption only in male mice. We detected an ethanol-induced overall decrease in hippocampal GFAPir and Iba1ir, independently of the treatment received, suggesting that RPTPβ/ζ is not key in the regulation of IAE-induced glial responses. However, we found a significant negative correlation between the size of microglial cells and the number of hippocampal neuronal progenitors only in male mice after IAE. This correlation was disrupted by treatment with MY10 before each drinking session, which may be related to the ability of MY10 to regulate the intensity of the perineuronal nets (PNNs) in the hippocampus in a sex-dependent manner. The data show for the first time that inhibition of RPTPβ/ζ reduces chronic voluntary ethanol consumption in adolescent mice in a sexdependent manner. In addition, we show evidence for sex-specific differences in the effects of IAE on glial responses and hippocampal neurogenesis, which may be related to different actions of the RPTPβ/ζ signalling pathway in the brains of male and female mice.
Description: En: Neuropharmacology ISSN. 0028-3908 n. 227 (2023)
URI: http://hdl.handle.net/10637/14115
Rights : http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
OpenAccess
ISSN: 1873-7064 (electrónico)
0028-3908
Supported by: Acuerdo Transformativo - 2023
Issue Date: 24-Jan-2023
Center : Universidad San Pablo-CEU
Appears in Collections:Facultad de Farmacia





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