The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age
Abstract
:1. Introduction
1.1. The Histone Families, H2A, and the DNA Damage Response
1.2. H2AX, Cell Cycle Checkpoints, and Genomic Instability
1.3. H2AX and Cell Growth
1.4. H2AX and Mitosis
1.5. H2AX and Embryogenesis
1.6. H2AX and Naturally Occurring DSBs in Gametes and Immune Cells
1.6.1. H2AX and Gametogenesis
1.6.2. H2AX and Lymphocyte Development
1.7. H2AX and Mitochondrial Homeostasis
1.8. H2AX and Apoptosis
1.9. H2AX and Hereditary Syndromes
1.10. H2AX and Tumors
2. H2AX in the Normal Brain
2.1. H2AX in the Develo** Brain
2.1.1. γH2AX in Embryonic Neurogenesis
2.1.2. γH2AX in Infantile Neurogenesis
2.1.2.1. SVZ/RMS/OB
2.1.2.2. Cerebellum
2.2. γH2AX in the Adult Brain
2.2.1. γH2AX in Adult Neurogenesis
Classical Neurogenetic Areas
Others
2.2.2. Cerebral Cortex
2.3. γH2AX in the Aging Brain
2.3.1. Neurogenic Areas
SVZ/RMS/OB
Hippocampus
2.3.2. Cerebral Cortex
3. γH2AX in the Experimentally Damaged Brain and Neuropathology
3.1. γH2AX and DNA Damaging Agents
3.1.1. Ionizing Radiations
3.1.2. Neurotoxic Substances
3.1.3. Oxidative Stress
3.1.4. Telomere Dysfunction
3.1.5. Injury
3.1.6. Neurologic Disorders
Alzheimer’s Disease (AD)
Huntington’s Disease (HD)
Parkinson’s Disease (PD)
Fragile X Syndrome
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)
Others
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Chemical/Drug | Experimental Target | Mechanism of Action | Other Effects besides Induction of γH2AX | References |
---|---|---|---|---|
Actinomycin D | Rat sensory ganglion neurons | Inhibition RNA synthesis | Heterochromatin silencing | [184] |
Ethanol | Mouse brain and human neuronal cells | Induction of apoptosis | Induction of FANCD2 | [185] |
Camptothecin | Rat cortical neurons | Inhibition of topoisomerase I with apoptosis | Activation of ATM, CHK2, MDC1, and 53BP1 | [186] |
Temozolomide | Human glioblastoma cell lines | Methylation of DNA guanine bases with apoptosis | N/A | [187] |
Mifepristone | Mouse photoreceptors | Glucocorticoid receptors antagonism | Induction of pro-apoptotic factors | [188] |
DSP4 | SHSY5Y cells | Block of noradrenaline uptake | Degeneration of noradrenergic terminals | [189] |
TCDD | SHSY5Y and PC12 cells | Activation of the aryl hydrocarbon receptor | Premature senescence | [190] |
Cisplatin, oxaliplatin, carboplatin | Cultured rat sensory neurons | Crosslink with the DNA urine bases with apoptosis | Reduction of the capsaicin-evoked release of CGRP | [191] |
Ara-C | Cultured mouse hippocampal neurons | Inhibition of DNA polymerases, block of cell mitosis | N/A | [192] |
Cypermethrin | Adult zebrafish retinal cells | Disruption of voltage-gated Na+ channel function | Increase of cCASP3 | [193] |
Zinc oxide nanoparticles | SHSY5Y cells | Viability decrease, apoptosis, cell cycle alterations DNA damage | Production of micronuclei | [194] |
Oxidative Stress Inducer | Experimental Target | Mechanism of Action | Other Effects besides Induction of γH2AX | References |
---|---|---|---|---|
Fluorescent immunohistochemical techniques | Cultured rat cortical neurons | Supra threshold activation of ionotropic glutamate receptors | Induction of MRE11 | [124] |
KA | Rat hippocampus and entorhinal cortex in vivo | Activation of KA receptors and induction of seizures | Induction of MRE11 | [195] |
NMDA | Mouse retinal ganglion cells and inner nuclear layer cells | Activation of NMDA receptors | Increase in 8-OHdG and TUNEL positive cells | [196] |
Hydrogen peroxide | BE(2)C neuroblastoma cells | Induction of oxidative stress | Change in cellular levels of MRE11, RAD50, nibrin, and ERCC1 | [197] |
Genetic mutation | Glucose-6-phosphate dehydrogenase-deficient mice | Reduction in NADPH levels | Synaptic and behavioral disorders | [198] |
Sevoflurane | In vitro and in vivo rat neurons | Decrease of gap junction mediated cell-cell coupling and alteration of the action potential | Increase of intracellular ROSNeuronal cell parthanatos | [199] |
TRESK silencing | Cultured mouse spinal cord dorsal horn neurons | Regulation of primary sensory neurons excitability | Induction of apoptosis | [200] |
Sterigmatocystin | Rat hippocampal DG | Induction of oxidative stress, mitochondrial dysfunction, apoptosis, cell cycle arrest | Disruption of postnatal neurogenesis and adult-stage suppression of synaptic plasticity | [201] |
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Merighi, A.; Gionchiglia, N.; Granato, A.; Lossi, L. The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age. Molecules 2021, 26, 7198. https://doi.org/10.3390/molecules26237198
Merighi A, Gionchiglia N, Granato A, Lossi L. The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age. Molecules. 2021; 26(23):7198. https://doi.org/10.3390/molecules26237198
Chicago/Turabian StyleMerighi, Adalberto, Nadia Gionchiglia, Alberto Granato, and Laura Lossi. 2021. "The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age" Molecules 26, no. 23: 7198. https://doi.org/10.3390/molecules26237198