Requirement of brain interleukin33 for aquaporin4 expression in astrocytes and glymphatic drainage of abnormal tau
| Autor: | João Quevedo, Colin Carlock, Yahuan Lou, Jean Wu, Tatiana Barichello, William F Glass, April Ross, Junbo Shim, Ines Moreno-Gonzalez |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
DNA repair Physiology Plaque Amyloid tau Proteins medicine.disease_cause Article law.invention 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine law Alzheimer Disease medicine Animals Molecular Biology Aquaporin 4 Chemistry Autophagy Neurodegeneration Brain medicine.disease Interleukin-33 Peripheral Cell biology Psychiatry and Mental health 030104 developmental biology Tauopathies Astrocytes Recombinant DNA Glymphatic system Tauopathy sense organs 030217 neurology & neurosurgery Oxidative stress Neuroscience |
| Zdroj: | Molecular Psychiatry |
| ISSN: | 1476-5578 1359-4184 |
| Popis: | Defective aquaporin4 (AQP4)-mediated glymphatic drainage has been linked to tauopathy and amyloid plaque in Alzheimer’s disease. We now show that brain interleukin33 (IL33) is required for regulation of AQP4 expression in astrocytes, especially those at neuron-facing membrane domain (n-AQP4). First, IL33-deficient (Il33−/−) mice showed a loss of n-AQP4 after middle age, which coincided with a rapid accumulation of abnormal tau in neurons and a reduction in drainage of abnormal tau to peripheral tissues. Second, injection of recombinant IL33 induced robust expression of AQP4 at perivascular endfoot (p-AQP4) of astrocytes, but not n-AQP4, in Il33−/− brains. Although the increased p-AQP4 greatly accelerated drainage of intracerebroventricularly injected peptides, it did not substantially accelerate drainage of abnormal tau. These results suggest that p-AQP4 drives overall convective flow toward perivenous space, i.e., glymphatics, whereas n-AQP4 may generate an aqueous flow away from neurons to remove neuronal wastes, e.g., abnormal tau. We have previously shown the role of brain IL33 in DNA repair and autophagy in neurons with oxidative stress. Now, we show that IL33 deficiency also impairs glymphatic drainage. Defects in those mechanisms together may lead to chronic neurodegeneration and tauopathy at old age in IL33-deficient mice. |
| Databáze: | OpenAIRE |
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