Digital Public Defence: Agnete Prydz
Cand.med. Agnete Prydz at Institute of Basic Medical Sciences will be defending the thesis "Detrimental synergy; Deciphering the roles of Aquaporins in Parkinson’s Disease" for the degree of PhD (Philosophiae Doctor).
Photo: Jon Olav Nesvold
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
An electronic copy of the thesis may be ordered from the faculty up to 2 days prior to the public defence. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture - time and place
- First opponent: Professor Alexej Verkhratsky, The University of Manchester, United Kingdom
- Second opponent: Associate Professor Lorenz Hirt, Lausanne University Hospital, Switzerland
- Third member and chair of the evaluation committee: Professor Sandip Kanse, Institute of Basic Medical Sciences, University of Oslo Norway
Chair of defence
Professor Emeritus Petter Laake, Institute of Basic Medical Sciences, University of Oslo
Professor Mahmood Amiry-Moghaddam, Institute of Basic Medical Sciences, University of Oslo
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive selective loss of dopaminergic neurons (DN) in substantia nigra pars compacta (SNpc). The etiology of PD is unknown, though environmental toxins and neuroinflammation are identified as potential key factors in the pathogenesis. The protein channels aquaporin 4 (AQP4) and aquaporin 9 (AQP9) are expressed in a variety of brain regions, including the SN, where AQP9 is found expressed in the DN. AQP4 is selectively permeable to water and has been coupled to several neurodegenerative diseases, where neuroinflammation is a common denominator. AQP9 is on the contrary permeable to a broad spectrum of solutes.
The aim of this thesis was to evaluate the potential pathophysiological roles of AQP4 and AQP9 in PD by focusing on glial aspects of neuroinflammation and toxic contribution. Using two different mouse models of PD, through subcutaneous and intrastriatal injections of the parkinsonogenic toxin MPTP/MPP+, we show that AQP4 is highly expressed in SNpc under physiological conditions and further increased in the PD mouse models. We show that treatment with MPP+ lead to upregulation of genes known to activate microglia in SNpc in WT mice and not in Aqp4-/- mice. WT mice showed higher degree of dopaminergic cell death. To investigate the theory that AQP9 functions as a gateway channel for parkinsonogenic toxins, we established AQP9 permeability to MPP+ by using Xenopus oocytes expressing AQP9. Targeted deletion of Aqp9 proved protective of dopaminergic cell death both in vitro and in vivo in the MPP+ mouse model.
In conclusion, this thesis has pinpointed AQP4 and AQP9 as detrimental factors in the
pathogenesis of PD, where AQP9 functions as a toxin facilitator enabling access to DN whereas AQP4 plays the role of toxin exacerbator, amplifying the toxic effect in SNpc through neuroinflammation. This novel insight in to the pathogenesis of PD, may pave the way for new therapeutic targets in PD.
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