Decreased AQP4 Expression Aggravates ɑ-Synuclein Pathology in Parkinson’s Disease Mice, Possibly via Impaired Glymphatic Clearance

Mar 27, 2021Journal of molecular neuroscience : MN

Lower AQP4 Levels May Worsen Parkinson’s Protein Build-up by Reducing Brain Waste Clearance in Mice

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Abstract

Decreased expression of aquaporin 4 (AQP4) accelerated pathologic deposition of α-synuclein in a Parkinson's disease model.

AQP4 null mice subjected to α-syn preformed fibrils exhibited increased α-syn pathology.
Loss of dopamine neurons and behavioral disorders were more pronounced in AQP4-deficient mice.
Decreased AQP4 expression is associated with slowed drainage of macromolecules from the brain.
Impairment of the glymphatic pathway may contribute to the observed aggravation of Parkinson's disease pathology.

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The pathological hallmarks of Parkinson's disease (PD), a neurodegenerative disorder, are the selective loss of dopamine neurons in the substantia nigra pars compacta (SNpc) and the presence of α-synuclein (α-syn) aggregates in the form of Lewy bodies/Lewy neurites (LBs/LNs) in neurons. Recent studies have indicated that aquaporin 4 (AQP4), as a predominant water channel protein in the brain, is involved in the progression of Parkinson's disease (PD). However, it remains unclear whether AQP4 expression affects α-syn pathology in Parkinson's disease. In this study, we established a progressive PD model by subjecting AQP4 null (AQP4) mice to bilateral intrastriatal injection of α-syn preformed fibrils (PFFs) and investigated the effect of decreased AQP4 expression on the development of PD. We found that decreased expression of AQP4 accelerated pathologic deposition of α-syn and facilitated the loss of dopamine neurons and behavioral disorders. Draining of macromolecules from the brain via the glymphatic pathway was slowed due to decreased AQP4 expression. Taken together, these findings indicate that decreased AQP4 expression may aggravate PD-like pathology, possibly via impairment of the glymphatic pathway. +/-

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Decreased AQP4 Expression Aggravates ɑ-Synuclein Pathology in Parkinson’s Disease Mice, Possibly via Impaired Glymphatic Clearance

Abstract

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