Next Article in Journal
Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor, Are Associated with Human Seminoma
Next Article in Special Issue
Resveratrol Partially Prevents Rotenone-Induced Neurotoxicity in Dopaminergic SH-SY5Y Cells through Induction of Heme Oxygenase-1 Dependent Autophagy
Previous Article in Journal
Egr-1 Upregulates Siva-1 Expression and Induces Cardiac Fibroblast Apoptosis
Previous Article in Special Issue
Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2014, 15(1), 1554-1573; doi:10.3390/ijms15011554

Phosphorylation of Histone H2AX in the Mouse Brain from Development to Senescence

1
Department of Veterinary Sciences, Università di Torino, Via Leonardo da Vinci 44, Grugliasco I-10095, Italy
2
Istituto Italiano di Neuroscienze (INN), Via Leonardo da Vinci 44, Grugliasco I-10095, Italy
Present address: Miltenyi Biotec GmbH, Bergisch Gladbach 51427, Germany
§
Present address: Istituto Italiano di Tecnologia (IIT), Genoa 16121, Italy
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 12 November 2013 / Revised: 30 December 2013 / Accepted: 10 January 2014 / Published: 21 January 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
View Full-Text   |   Download PDF [2771 KB, uploaded 19 June 2014]   |  

Abstract

Phosphorylation of the histone H2AX (γH2AX form) is an early response to DNA damage and a marker of aging and disease in several cells and tissues outside the nervous system. Little is known about in vivo phosphorylation of H2AX in neurons, although it was suggested that γH2AX is an early marker of neuronal endangerment thus opening the possibility to target it as a neuroprotective strategy. After experimental labeling of DNA-synthesizing cells with 5-bromo-2-deoxyuridine (BrdU), we studied the brain occurrence of γH2AX in developing, postnatal, adult and senescent (2 years) mice by light and electron microscopic immunocytochemistry and Western blotting. Focal and/or diffuse γH2AX immunostaining appears in interkinetic nuclei, mitotic chromosomes, and apoptotic nuclei. Immunoreactivity is mainly associated with neurogenetic areas, i.e., the subventricular zone (SVZ) of telencephalon, the cerebellar cortex, and, albeit to a much lesser extent, the subgranular zone of the hippocampal dentate gyrus. In addition, γH2AX is highly expressed in the adult and senescent cerebral cortex, particularly the piriform cortex. Double labeling experiments demonstrate that γH2AX in neurogenetic brain areas is temporally and functionally related to proliferation and apoptosis of neuronal precursors, i.e., the type C transit amplifying cells (SVZ) and the granule cell precursors (cerebellum). Conversely, γH2AX-immunoreactive cortical neurons incorporating the S phase-label BrdU do not express the proliferation marker phosphorylated histone H3, indicating that these postmitotic cells undergo a significant DNA damage response. Our study paves the way for a better comprehension of the role of H2AX phosphorylation in the normal brain, and offers additional data to design novel strategies for the protection of neuronal precursors and mature neurons in central nervous system (CNS) degenerative diseases.
Keywords: H2AX; histone; DNA damage; immunocytochemistry; cell proliferation; apoptosis; neuroprotection; Alzheimer’s disease; Huntington’s disease H2AX; histone; DNA damage; immunocytochemistry; cell proliferation; apoptosis; neuroprotection; Alzheimer’s disease; Huntington’s disease
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Barral, S.; Beltramo, R.; Salio, C.; Aimar, P.; Lossi, L.; Merighi, A. Phosphorylation of Histone H2AX in the Mouse Brain from Development to Senescence. Int. J. Mol. Sci. 2014, 15, 1554-1573.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top