@article{60357285d9e44c59a3ab5afb7dbf2276,
title = "Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease",
abstract = "Histone deacetylase (HDAC) inhibitors have been widely reported to have considerable therapeutic potential in a host of neurodegenerative diseases. However, HDAC inhibitor selectivity and specificity in specific cell classes have been a source of much debate. To address the role of HDAC2 in specific cell classes, and in disease, we examined glial protein and mRNA levels in the substantia nigra (SN) of Parkinson's disease (PD) and normal controls (NCs) by immunohistochemistry and laser captured microdissection followed by quantitative real time polymerase chain reaction. Differential expression analysis in immunohistochemically defined laser capture microglia revealed significant upregulation of HDAC2 in the PD SN compared to NC subjects. Complementary in vivo evidence reveals significant upregulation of HDAC2 protein levels in PD SN microglia compared to NC subjects. Correspondingly, human immortalized telencephalic/mesencephalic microglial cells reveal significant upregulation of HDAC2 in the presence of the potent microglial activator lipopolysaccharide. These data provide evidence that selective inhibition of HDAC2 in PD SN microglia could be a promising approach to treat microglial-initiated nigral dopaminergic neuronal cell loss in PD.",
author = "Yuyan Tan and Elaine Delvaux and Jennifer Nolz and Paul Coleman and Shengdi Chen and Diego Mastroeni",
note = "Funding Information: This work was supported by National Natural Science Fund of China (81430022, 81100952), 5R01AG036400 PDC and NIRG-15-321390 and ADHS16-104646 fy2015-16 to D.M. The authors thank Dr. Thomas Beach, Lucia Sue, Dr. Geidy Serrano, and their staff for provision of tissue samples and postmortem evaluations. The brain bank is funded by the Arizona Study for Aging and Neurodegenerative Disorders and is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium), the Michael J. Fox Foundation for Parkinson's Research, the Mayo Clinic Foundation, and the Sun Health Foundation. The authors also thank the Arizona Alzheimer's Consortium, the National Institute on Aging (AG002132 Core C), the CurePSP Foundation, the Alzheimer's Association, the Henry M. Jackson Foundation (HU0001-15-2-0020), Daiichi Sankyo Co, Ltd, the National Institute of Mental Health (R01MH106674), and the National Institute of Biomedical Imaging and Bioengineering (R01EB021711) for funding, the Banner Brain and Body Donation Program for making the data available, and the many individuals who contributed their brains to make this study possible. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = aug,
doi = "10.1016/j.neurobiolaging.2018.02.018",
language = "English (US)",
volume = "68",
pages = "134--141",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}