Galán-Llario Milagros, Rodríguez-Zapata María, Fontán-Baselga Teresa, Cañeque-Rufo Héctor, García-Guerra Alba, Fernández Beatriz, Gramage Esther, Herradón Gonzalo
Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad san Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, Spain.
Instituto Universitario de Estudios de Las Adicciones, Universidad san Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, Spain.
CNS Neurosci Ther. 2024 Dec;30(12):e70159. doi: 10.1111/cns.70159.
To investigate whether pleiotrophin (PTN) overexpression influences ethanol consumption during adolescence and its effects on glial responses, neurogenesis, and perineuronal nets (PNNs) in the mouse hippocampus.
Male and female adolescent transgenic mice with elevated PTN levels (Ptn-Tg) and controls underwent an intermittent access to ethanol (IAE) 2-bottle choice protocol. Ethanol consumption, PTN levels, neurogenesis, and glial responses were measured in the hippocampus. Immunohistochemistry was used to assess changes in new neurons, microglial and astrocyte populations, and PNNs.
Ptn-Tg mice consumed significantly less ethanol compared to controls, irrespective of sex. Chronic alcohol exposure reduced PTN levels in the hippocampus. PTN overexpression decreased the number of new neurons in the dentate gyrus (DG) and prevented ethanol-induced microglial activation. Ptn-Tg mice had significantly more astrocytes and fewer PNNs, with a higher percentage of parvalbumin (PV) positive cells surrounded by PNNs under basal conditions. However, ethanol drastically reduced the number of PV+ cells in the DG of Ptn-Tg mice, despite the presence of PNNs.
PTN overexpression reduces adolescent ethanol consumption and influences ethanol-induced effects on hippocampal neurogenesis, glial responses, and PNN remodeling. These findings underscore the importance of PTN in modulating alcohol-induced neurotoxicity.
研究多效生长因子（PTN）过表达是否会影响青春期小鼠的乙醇摄取，以及其对小鼠海马体中神经胶质反应、神经发生和神经元周围网（PNN）的影响。
PTN水平升高的雄性和雌性青春期转基因小鼠（Ptn-Tg）及其对照小鼠接受间歇性乙醇摄入（IAE）两瓶选择方案。测量海马体中的乙醇摄取量、PTN水平、神经发生和神经胶质反应。采用免疫组织化学法评估新神经元、小胶质细胞和星形胶质细胞数量以及PNN的变化。
无论性别如何，Ptn-Tg小鼠的乙醇摄取量均显著低于对照小鼠。慢性酒精暴露会降低海马体中的PTN水平。PTN过表达会减少齿状回（DG）中新神经元的数量，并阻止乙醇诱导的小胶质细胞活化。在基础条件下，Ptn-Tg小鼠的星形胶质细胞显著增多，PNN减少，被PNN包围的小白蛋白（PV）阳性细胞百分比更高。然而，尽管存在PNN，乙醇仍会大幅减少Ptn-Tg小鼠DG中PV+细胞的数量。
PTN过表达会减少青春期小鼠的乙醇摄取，并影响乙醇对海马体神经发生、神经胶质反应和PNN重塑的诱导作用。这些发现强调了PTN在调节酒精诱导的神经毒性中的重要性。
