The Neuroscience Journal of Shefaye Khatam
مجله علوم اعصاب شفای خاتم
Shefaye Khatam
Medical Sciences
http://shefayekhatam.ir
1
admin
2322-1887
2345-4814
10.61186/shefa
fa
jalali
1396
1
1
gregorian
2017
4
1
5
2
online
1
fulltext
en
O 3:Therapeutic Potential of a Novel NMDA Receptor Subunit 2B Antagonist in a Mouse Model of Autoimmune Neuroinflammation
O 3:Therapeutic Potential of a Novel NMDA Receptor Subunit 2B Antagonist in a Mouse Model of Autoimmune Neuroinflammation
تحقیقات پایه در علوم اعصاب
Basic research in Neuroscience
مروری
Review --- Open Access, CC-BY-NC
<p style="text-align: center;"><span style="color: rgb(0, 0, 0); font-family: Tahoma; font-size: 12px; text-align: center; background-color: rgb(251, 250, 249);">لطفاً به چکیده انگلیسی مراجعه شود.</span></p>
<p>Glutamate-mediated excitotoxicity and neurodegeneration have been shown as pathophysiological hallmarks of multiple sclerosis (MS) and other autoimmune inflammatory CNS disorders. N‑Methyl‑D‑Aspartate (NMDA) receptors play a pivotal role in the mediation of neuronal glutamate excitotoxicity leading to cellular damage and apoptotic cell death. Current treatment approaches targeting glutamate excitotoxicity are unspecific and associated with severe adverse events due to the broad and important functions of NMDA receptors in the CNS. Hence, the present study investigates the neuroprotective potential of a novel specific NMDA receptor 2B (GluN2B) subunit antagonist. Prophylactic and therapeutic treatment with the GluN2B antagonist WMS14-10 (WMS) significantly ameliorated the disease course in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE), a murine model of MS. At disease maximum microglia from WMS treated mice showed decreased CD86 expression indicating reduced microglial activation. In agreement, activated microglia expressed GluN2B. Under restimulation with MOG splenocytes from WMS treated mice demonstrated decreased secretion of TNFα, INFγ and IL-17. In vitro WMS showed no significant effects on the function of T cells and macrophages/monocytes. However, incubation with WMS reduced lipopolysaccharide (LPS)-mediated secretion of cytokines like GM-CSF, IL-1α and TNFα by microglia. In conclusion, our results indicate that specific inhibition of GluN2B in microglia cells displays a newly identified pathway in neuroinflammatory degeneration. Ongoing studies aim at dissecting the underlying mechanisms and a putative additional effect on neuronal glutamate excitotoxicity.</p>
Therapeutic, Inflammatory, Mice
3
3
http://shefayekhatam.ir/browse.php?a_code=A-10-24-821&slc_lang=en&sid=1
Sarah
Glumm
Sarah
Glumm
sarah.glumm@ukmuenster.de
100319475328460011699
100319475328460011699
Yes
Department of Translational Neurology, University of Münster, Münster, Germany
Department of Translational Neurology, University of Münster, Münster, Germany
Tobias
Ruck
Tobias
Ruck
100319475328460011700
100319475328460011700
No
Department of Translational Neurology, University of Münster, Münster, Germany
Department of Translational Neurology, University of Münster, Münster, Germany
Dirk
Schepmann
Dirk
Schepmann
100319475328460011701
100319475328460011701
No
Department of Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany
Department of Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany
Heinz
Wiendl
Heinz
Wiendl
100319475328460011702
100319475328460011702
No
Department of Translational Neurology, University of Münster, Münster, Germany
Department of Translational Neurology, University of Münster, Münster, Germany
Bernhard
Wünsch
Bernhard
Wünsch
100319475328460011703
100319475328460011703
No
Department of Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany
Department of Pharmaceutical and Medical Chemistry, University of Münster, Münster, Germany
Stefan
Bittner
Stefan
Bittner
100319475328460011704
100319475328460011704
No
Department of Neurology, University of Mainz, Mainz, Germany
Department of Neurology, University of Mainz, Mainz, Germany
Sven G
Meuth
Sven G
Meuth
100319475328460011705
100319475328460011705
No
Department of Translational Neurology, University of Münster, Münster, Germany
Department of Translational Neurology, University of Münster, Münster, Germany