Pleiotrophin Overexpression Reduces Adolescent Ethanol Consumption and Modulates Ethanol-Induced Glial Responses and Changes in the Perineuronal Nets in the Mouse Hippocampus.

Aims: 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.

Methods: 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.

Implication of the PTN/RPTPβ/ζ Signaling Pathway in Acute Ethanol Neuroinflammation in Both Sexes: A Comparative Study with LPS.

Binge drinking during adolescence increases the risk of alcohol use disorder, possibly by involving alterations of neuroimmune responses. Pleiotrophin (PTN) is a cytokine that inhibits Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ. PTN and MY10, an RPTPβ/ζ pharmacological inhibitor, modulate ethanol behavioral and microglial responses in adult mice.

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.

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.

Receptor protein tyrosine phosphatase β/ζ regulates loss of neurogenesis in the mouse hippocampus following adolescent acute ethanol exposure.

Adolescence 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.