title: Morphine Withdrawal Modifies Prion Protein Expression in Rat Hippocampus.
abstract: The hippocampus is a vulnerable brain structure susceptible to damage during aging and chronic stress. Repeated exposure to opioids may alter the brain so that it functions normally when the drugs are present, thus, a prolonged withdrawal might lead to homeostatic changes headed for the restoration of the physiological state. Abuse of morphine may lead to Reacting Oxygen Species-induced neurodegeneration and apoptosis. It has been proposed that during morphine withdrawal, stress responses might be responsible, at least in part, for long-term changes of hippocampal plasticity. Since prion protein is involved in both, Reacting Oxygen Species mediated stress responses and synaptic plasticity, in this work we investigate the effect of opiate withdrawal in rats after morphine treatment. We hypothesize that stressful stimuli induced by opiate withdrawal, and the subsequent long-term homeostatic changes in hippocampal plasticity, might modulate the Prion protein expression. Our results indicate that abstinence from the opiate induced a time-dependent and region-specific modification in Prion protein content, indeed during morphine withdrawal a selective unbalance of hippocampal Prion Protein is observable. Moreover, Prion protein overexpression in hippocampal tissue seems to generate a dimeric structure of Prion protein and α-cleavage at the hydrophobic domain. Stress factors or toxic insults can induce cytosolic dimerization of Prion Protein through the hydrophobic domain, which in turn, it stimulates the α-cleavage and the production of neuroprotective Prion protein fragments. We speculate that this might be the mechanism by which stressful stimuli induced by opiate withdrawal and the subsequent long-term homeostatic changes in hippocampal plasticity, modulate the expression and the dynamics of Prion protein.
authors.affiliation: Laboratorio di Medicina Sperimentale e Patologia Ambientale, Polo Universitario di Rieti "Sabina Universitas", Rieti, Italia.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mattei
authors.affiliation: Laboratorio di Medicina Sperimentale e Patologia Ambientale, Polo Universitario di Rieti "Sabina Universitas", Rieti, Italia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Martellucci
authors.affiliation: Laboratorio di Medicina Sperimentale e Patologia Ambientale, Polo Universitario di Rieti "Sabina Universitas", Rieti, Italia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Valeria
authors.initials: V
authors.lastname: Manganelli
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Tina
authors.initials: T
authors.lastname: Garofalo
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Niccolò
authors.initials: N
authors.lastname: Candelise
authors.affiliation: Dipartimento di Fisiologia e Farmacologia "Vittorio Erspamer", Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Caruso
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.affiliation: Dipartimento di Fisiologia e Farmacologia "Vittorio Erspamer", Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Sergio
authors.initials: S
authors.lastname: Scaccianoce
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Roma "La Sapienza", Roma, Italia.
authors.forename: Roberta
authors.identifier: http://orcid.org/0000-0002-1181-6190
authors.initials: R
authors.lastname: Misasi
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism* / Q000473:pathology; D000072002:Prion Proteins / Q000096:biosynthesis*; D000072417:Protein Domains; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000473:pathology
chemical_list: D000072002:Prion Proteins; D017382:Reactive Oxygen Species