Histone deacetylase inhibitors preserve function in aging axons.
Aging increases the vulnerability of aging white matter to ischemic injury. Histone deacetylase (HDAC) inhibitors preserve young adult white matter structure and function during ischemia by conserving ATP and reducing excitotoxicity. In isolated optic nerve from 12-month-old mice, deprived of oxygen and glucose, we show that pan- and Class I-specific HDAC inhibitors promote functional recovery of axons. This protection correlates with preservation of axonal mitochondria. The cellular expression of HDAC 3 in the central nervous system (CNS), and HDAC 2 in optic nerve considerably changed with age, expanding to more cytoplasmic domains from nuclear compartments, suggesting that changes in glial cell protein acetylation may confer protection to aging axons. Our results indicate that manipulation of HDAC activities in glial cells may have a universal potential for stroke therapy across age groups.
Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. baltans@ccf.org
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Baltan
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009900:Optic Nerve / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D000077337:Vorinostat
D001549:Benzamides; C485182:Cyan Fluorescent Protein; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011725:Pyridines; D049452:Green Fluorescent Proteins; C118739:entinostat; D000077337:Vorinostat; D006655:Histone Deacetylases; D005947:Glucose