title: Localization and regulation of PML bodies in the adult mouse brain.
abstract: PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons.
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Małgorzata H
authors.initials: MH
authors.lastname: Hall
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Magalska
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Malinowska
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Błażej
authors.initials: B
authors.lastname: Ruszczycki
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Czaban
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester, LE1 7RH, UK.
authors.forename: Satyam
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Clinical Cytology, Center of Postgraduate Medical Education, Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ambrożek-Latecka
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zołocińska
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Broszkiewicz
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Parobczak
authors.affiliation: Neuroscience Research Group, Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway.
authors.forename: Rajeevkumar R
authors.initials: RR
authors.lastname: Nair
authors.affiliation: Department of Clinical Cytology, Center of Postgraduate Medical Education, Marymoncka 99/103, 01-813, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Rylski
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester, LE1 7RH, UK.|Hatherley Laboratories, University of Exeter Medical School, Prince of Wales Road, Exeter, EX4 4PS, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Pawlak
authors.affiliation: Neuroscience Research Group, Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bramham
authors.affiliation: Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland. g.wilczynski@nencki.gov.pl.
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczyński
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism; D012640:Seizures / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism
chemical_list: C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein
keywords: Brain; Cell nucleus; Cerebral cortex; Nuclear body; PML; Promyelocytic leukemia; Seizures; Stress