The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain

Stayte, S; Laloli, KJ; Rentsch, P; Lowth, A; Li, KM; Pickford, R; Vissel, B

The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain

Stayte, S

Laloli, KJ Rentsch, P Lowth, A Li, KM Pickford, R Vissel, B

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Publication Type:: Journal Article
Citation:: Experimental Neurology, 2020, 323
Issue Date:: 2020-01-01

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Field	Value	Language
dc.contributor.author	Stayte, S https://orcid.org/0000-0002-6518-1979	en_US
dc.contributor.author	Laloli, KJ	en_US
dc.contributor.author	Rentsch, P	en_US
dc.contributor.author	Lowth, A	en_US
dc.contributor.author	Li, KM	en_US
dc.contributor.author	Pickford, R	en_US
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050	en_US
dc.date.available	2021-01-02T18:05:56Z
dc.date.issued	2020-01-01	en_US
dc.identifier.citation	Experimental Neurology, 2020, 323	en_US
dc.identifier.issn	0014-4886	en_US
dc.identifier.uri	http://hdl.handle.net/10453/136564
dc.description.abstract	© 2019 Elsevier Inc. The excitatory neurotransmitter glutamate is essential in basal ganglia motor circuits and has long been thought to contribute to cell death and degeneration in Parkinson's disease (PD). While previous research has shown a significant role of NMDA and AMPA receptors in both excitotoxicity and PD, the third class of ionotropic glutamate receptors, kainate receptors, have been less well studied. Given the expression of kainate receptor subunits GluK1-GluK3 in key PD-related brain regions, it has been suggested that GluK1-GluK3 may contribute to excitotoxic cell loss. Therefore the neuroprotective potential of the kainate receptor antagonist UBP310 in animal models of PD was investigated in this study. Stereological quantification revealed administration of UBP310 significantly increased survival of dopaminergic and total neuron populations in the substantia nigra pars compacta in the acute MPTP mouse model of PD. In contrast, UBP310 was unable to rescue MPTP-induced loss of dopamine levels or dopamine transporter expression in the striatum. Furthermore, deletion of GluK1, GluK2 or GluK3 had no effect on MPTP or UBP310-mediated effects across all measures. Interestingly, UBP310 did not attenuate cell loss in the midbrain induced by intrastriatal 6-OHDA toxicity. These results indicate UBP310 provides neuroprotection in the midbrain against MPTP neurotoxicity that is not dependent on specific kainate receptor subunits.	en_US
dc.relation.ispartof	Experimental Neurology	en_US
dc.relation.isbasedon	10.1016/j.expneurol.2019.113062	en_US
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.title	The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain	en_US
dc.type	Journal Article
utslib.citation.volume	323	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1701 Psychology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
pubs.publication-status	Published	en_US
pubs.volume	323	en_US

Abstract:

© 2019 Elsevier Inc. The excitatory neurotransmitter glutamate is essential in basal ganglia motor circuits and has long been thought to contribute to cell death and degeneration in Parkinson's disease (PD). While previous research has shown a significant role of NMDA and AMPA receptors in both excitotoxicity and PD, the third class of ionotropic glutamate receptors, kainate receptors, have been less well studied. Given the expression of kainate receptor subunits GluK1-GluK3 in key PD-related brain regions, it has been suggested that GluK1-GluK3 may contribute to excitotoxic cell loss. Therefore the neuroprotective potential of the kainate receptor antagonist UBP310 in animal models of PD was investigated in this study. Stereological quantification revealed administration of UBP310 significantly increased survival of dopaminergic and total neuron populations in the substantia nigra pars compacta in the acute MPTP mouse model of PD. In contrast, UBP310 was unable to rescue MPTP-induced loss of dopamine levels or dopamine transporter expression in the striatum. Furthermore, deletion of GluK1, GluK2 or GluK3 had no effect on MPTP or UBP310-mediated effects across all measures. Interestingly, UBP310 did not attenuate cell loss in the midbrain induced by intrastriatal 6-OHDA toxicity. These results indicate UBP310 provides neuroprotection in the midbrain against MPTP neurotoxicity that is not dependent on specific kainate receptor subunits.

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http://hdl.handle.net/10453/136564