Session Information
Date: Tuesday, June 6, 2017
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: Supporting by glial cells could be reinforced the function of dopaminergic neurons against extracellular insults in Parkinson’s disease (PD) development. However, we do not understand the molecular pathway that how they modulate the dopaminergic neurons via the actions of activated astrocytes and cytokines. We focused on the dopaminergic neurons and investigated underlying mechanism of tyrosine hydroxylase (TH) modulation in acute methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model.
Background: High-mobility group box 1 (HMGB1) can be actively secreted from inflammatory cells and is known to both promote inflammation and protect against disease propagation. Also, HMGB1 act as a mediator of neuroinflammation in subacute PD animal model.
Methods: Male C57Bl/6 mice were intraperitoneal injections of sterile saline or MPTP administered as 4 times injections of 20mg/kg at 2h intervals and were sacrificed at selected time points after the last injection (1, 3, 5 and 7 days). We measured by enzyme-linked immunosorbent assay (ELISA) that detects HMGB1 in human PD patient serum and U87MG cells (human a glioblastoma, astrocytoma cell line).
Results: The staining intensities of HMGB1 and Receptor for advanced glycation end product (RAGE) are higher in the nigral area of MPTP-treated mice, a toxin-induced PD like model, compared to saline-treated controls. HMGB1 was found to principally localize to astrocytes, and could affect the neighboring dopaminergic neurons, due to co-localization of RAGE with TH-positive cells. Treatment of a dopaminergic neuron cells with HMGB1 simultaneously induced JNK phosphorylation and TH mRNA expression. A JNK inhibitor was found to block the HMGB1-induced upregulation of TH expression.
Conclusions: Our results suggest that increased HMGB1 in astrocytes upregulates TH expression to maintain dopaminergic neuronal functions in acute MPTP mouse model. And HMGB1 could be a new research target for modulation of dopaminergic neurons.
References: Lotze, M. T., & Tracey, K. J. (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol, 5(4), 331-342.
To cite this abstract in AMA style:
S.J. Kim, M.J. Ryu, J. Han, Y. Jang, J. Kim, M.J. Lee, I. Ryu, X. Ju, W. Chung, E. Oh, G.R. Kweon. High-mobility group box 1 from astrocytes upregulates TH expression to maintain dopaminergic neurons via JNK pathway in human Parkinson’s disease patients and MPTP induced mouse model [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/high-mobility-group-box-1-from-astrocytes-upregulates-th-expression-to-maintain-dopaminergic-neurons-via-jnk-pathway-in-human-parkinsons-disease-patients-and-mptp-induced-mouse-model/. Accessed June 14, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/high-mobility-group-box-1-from-astrocytes-upregulates-th-expression-to-maintain-dopaminergic-neurons-via-jnk-pathway-in-human-parkinsons-disease-patients-and-mptp-induced-mouse-model/