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Localization of the Locus Coeruleus in the Mouse Brain
Published on: March 7, 2019
Localization and regulation of PML bodies in the adult mouse brain
Małgorzata H Hall1, Adriana Magalska1, Monika Malinowska1
1Laboratory of Molecular and Systemic Neuromorphology, Department of Neurophysiology, Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland.
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.
Insights
Promyelocytic leukemia protein (PML) nuclear bodies are found in adult mouse neurons, particularly in the cerebral and cerebellar cortices. Their formation and characteristics are influenced by stress and seizures, suggesting a role in neuronal activity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- The promyelocytic leukemia (PML) protein is a tumor suppressor, forming nuclear bodies in non-neuronal cells.
- PML's role in the adult brain, including its localization and nuclear body presence, remains incompletely understood.
- PML is implicated in embryonic neurogenesis and adult brain physiological/pathological processes.
Purpose of the Study:
- To investigate the anatomical distribution and cellular localization of PML protein and its associated nuclear bodies in the adult mouse brain.
- To characterize the ultrastructural features of neuronal PML bodies.
- To explore the dynamic regulation of neuronal PML bodies.
Main Methods:
- Immunohistochemistry and immunofluorescence in adult mouse brain sections.
- Confocal and electron microscopy for ultrastructural analysis.
- Assessment of PML body changes under stress and seizure conditions.
Main Results:
- PML is broadly expressed in gray matter, with high levels in cerebral and cerebellar cortices.
- In the cerebral cortex, PML is exclusively in neurons, forming nuclear inclusions with SUMO-1/2/3 but not Daxx.
- Neuronal PML bodies differ ultrastructurally from classic PML bodies, appearing as small aggregates near chromatin, and are dynamically modulated by stress and seizures.
Conclusions:
- PML nuclear bodies are present and broadly distributed in adult mouse neurons.
- Neuronal PML bodies exhibit unique ultrastructural features and are sensitive to neuronal activity.
- These findings suggest PML bodies are involved in activity-dependent nuclear events in adult neurons.
