Title | Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Xu Z, Xiao N, Chen Y, Huang H, Marshall C, Gao J, Cai Z, Wu T, Hu G, Xiao M |
Journal | Mol Neurodegener |
Volume | 10 |
Pagination | 58 |
Date Published | 2015 Nov 02 |
ISSN | 1750-1326 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Animals, Aquaporin 4, Brain, Brain-Derived Neurotrophic Factor, Cerebral Amyloid Angiopathy, Cognition Disorders, Inflammation, Memory Disorders, Mice, Transgenic |
Abstract | BACKGROUND: Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer's disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent. RESULTS: Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignificant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples. CONCLUSIONS: These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD. |
DOI | 10.1186/s13024-015-0056-1 |
Alternate Journal | Mol Neurodegener |
PubMed ID | 26526066 |
PubMed Central ID | PMC4631089 |