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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 134-141 |
| Number of pages | 8 |
| Journal | Neurobiology of Aging |
| Volume | 68 |
| DOIs | |
| State | Published - Aug 1 2018 |
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ASJC Scopus subject areas
- Neuroscience(all)
- Aging
- Clinical Neurology
- Developmental Biology
- Geriatrics and Gerontology
Cite this
Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease. / Tan, Yuyan; Delvaux, Elaine; Nolz, Jennifer; Coleman, Paul; Chen, Shengdi; Mastroeni, Diego.
In: Neurobiology of Aging, Vol. 68, 01.08.2018, p. 134-141.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease
AU - Tan, Yuyan
AU - Delvaux, Elaine
AU - Nolz, Jennifer
AU - Coleman, Paul
AU - Chen, Shengdi
AU - Mastroeni, Diego
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047273067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047273067&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2018.02.018
DO - 10.1016/j.neurobiolaging.2018.02.018
M3 - Article
C2 - 29803514
AN - SCOPUS:85047273067
VL - 68
SP - 134
EP - 141
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
ER -