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Article

Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+

by
Agnete Prydz
1,†,
Katja Stahl
1,†,
Soulmaz Zahl
1,
Nadia Skauli
1,
Øivind Skare
2,
Ole Petter Ottersen
3 and
Mahmood Amiry-Moghaddam
1,*
1
Laboratory of Molecular Neuroscience, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1105, Blindern, 0317 Oslo, Norway
2
Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, Gydas vei 8, 0363 Oslo, Norway
3
President’s Office, Karolinska Institutet, Nobels väg 6, 171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
†
These authors have contributed equally.
Cells 2020, 9(11), 2418; https://doi.org/10.3390/cells9112418
Submission received: 14 October 2020 / Revised: 1 November 2020 / Accepted: 2 November 2020 / Published: 5 November 2020
(This article belongs to the Special Issue Advances in Aquaporins)
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Abstract

Aquaporin-4 (AQP4) is critically involved in brain water and volume homeostasis and has been implicated in a wide range of pathological conditions. Notably, evidence has been accrued to suggest that AQP4 plays a proinflammatory role by promoting release of astrocytic cytokines that activate microglia and other astrocytes. Neuroinflammation is a hallmark of Parkinson’s disease (PD), and we have previously shown that astrocytes in substantia nigra (SN) are enriched in AQP4 relative to cortical astrocytes, and that their complement of AQP4 is further increased following treatment with the parkinsonogenic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Here, we investigated the effect of Aqp4 deletion on microglial activation in mice subjected to unilateral intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP+, the toxic metabolite of MPTP). Our results show that MPP+ injections lead to a pronounced increase in the expression level of microglial activating genes in the ventral mesencephalon of wild type (WT) mice, but not Aqp4−/− mice. We also show, in WT mice, that MPP+ injections cause an upregulation of nigral AQP4 and swelling of astrocytic endfeet. These findings are consistent with the idea that AQP4 plays a pro-inflammatory role in Parkinson’s disease, secondary to the dysregulation of astrocytic volume homeostasis.
Keywords: AQP4; Parkinson’s disease; MPP+; astrocyte; microglia; neuroinflammation AQP4; Parkinson’s disease; MPP+; astrocyte; microglia; neuroinflammation
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MDPI and ACS Style

Prydz, A.; Stahl, K.; Zahl, S.; Skauli, N.; Skare, Ø.; Ottersen, O.P.; Amiry-Moghaddam, M. Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+. Cells 2020, 9, 2418. https://doi.org/10.3390/cells9112418

AMA Style

Prydz A, Stahl K, Zahl S, Skauli N, Skare Ø, Ottersen OP, Amiry-Moghaddam M. Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+. Cells. 2020; 9(11):2418. https://doi.org/10.3390/cells9112418

Chicago/Turabian Style

Prydz, Agnete, Katja Stahl, Soulmaz Zahl, Nadia Skauli, Øivind Skare, Ole Petter Ottersen, and Mahmood Amiry-Moghaddam. 2020. "Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+" Cells 9, no. 11: 2418. https://doi.org/10.3390/cells9112418

APA Style

Prydz, A., Stahl, K., Zahl, S., Skauli, N., Skare, Ø., Ottersen, O. P., & Amiry-Moghaddam, M. (2020). Pro-Inflammatory Role of AQP4 in Mice Subjected to Intrastriatal Injections of the Parkinsonogenic Toxin MPP+. Cells, 9(11), 2418. https://doi.org/10.3390/cells9112418

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