Locomotor Hyperactivity in the Early-Stage Alzheimer’s Disease-like Pathology of APP/PS1 Mice: Associated with Impaired Polarization of Astrocyte Aquaporin 4 Article Swipe
Tianqi Wang
,
Yan Chen
,
Ying Zou
,
Yingting Pang
,
Xiaoxin He
,
Yali Chen
,
Yun Liu
,
Weixi Feng
,
Yanli Zhang
,
Qian Li
,
Jingping Shi
,
Fengfei Ding
,
Charles Marshall
,
Junying Gao
,
Ming Xiao
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.14336/ad.2022.0219
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.14336/ad.2022.0219
Non-cognitive behavioral and psychological symptoms often occur in Alzheimer's disease (AD) patients and mouse models, although the exact neuropathological mechanism remains elusive. Here, we report hyperactivity with significant inter-individual variability in 4-month-old APP/PS1 mice. Pathological analysis revealed that intraneuronal accumulation of amyloid-β (Aβ), c-Fos expression in glutamatergic neurons and activation of astrocytes were more evident in the frontal motor cortex of hyperactive APP/PS1 mice, compared to those with normal activity. Moreover, the hyperactive phenotype was associated with mislocalization of perivascular aquaporin 4 (AQP4) and glymphatic transport impairment. Deletion of the AQP4 gene increased hyperactivity, intraneuronal Aβ load and glutamatergic neuron activation, but did not influence working memory or anxiety-like behaviors of 4-month-old APP/PS1 mice. Together, these results demonstrate that AQP4 mislocalization or deficiency leads to increased intraneuronal Aβ load and neuronal hyperactivity in the motor cortex, which in turn causes locomotor over-activity during the early pathophysiology of APP/PS1 mice. Therefore, improving AQP4 mediated glymphatic clearance may offer a new strategy for early intervention of hyperactivity in the prodromal phase of AD.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.14336/ad.2022.0219
- OA Status
- gold
- Cited By
- 34
- References
- 83
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4295559738
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4295559738Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.14336/ad.2022.0219Digital Object Identifier
- Title
-
Locomotor Hyperactivity in the Early-Stage Alzheimer’s Disease-like Pathology of APP/PS1 Mice: Associated with Impaired Polarization of Astrocyte Aquaporin 4Work title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
-
2022-01-01Full publication date if available
- Authors
-
Tianqi Wang, Yan Chen, Ying Zou, Yingting Pang, Xiaoxin He, Yali Chen, Yun Liu, Weixi Feng, Yanli Zhang, Qian Li, Jingping Shi, Fengfei Ding, Charles Marshall, Junying Gao, Ming XiaoList of authors in order
- Landing page
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https://doi.org/10.14336/ad.2022.0219Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.14336/ad.2022.0219Direct OA link when available
- Concepts
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Aquaporin 4, Glutamatergic, Astrocyte, Neuroscience, Medicine, Disease, Psychology, Pathology, Internal medicine, Central nervous system, Glutamate receptor, ReceptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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34Total citation count in OpenAlex
- Citations by year (recent)
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2025: 13, 2024: 15, 2023: 6Per-year citation counts (last 5 years)
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83Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.turn | 138 |
| abstract_inverted_index.were | 52 |
| abstract_inverted_index.with | 26, 67, 76 |
| abstract_inverted_index.Here, | 22 |
| abstract_inverted_index.c-Fos | 43 |
| abstract_inverted_index.early | 144, 161 |
| abstract_inverted_index.exact | 17 |
| abstract_inverted_index.leads | 123 |
| abstract_inverted_index.mice, | 63 |
| abstract_inverted_index.mice. | 33, 113, 148 |
| abstract_inverted_index.motor | 58, 134 |
| abstract_inverted_index.mouse | 13 |
| abstract_inverted_index.occur | 6 |
| abstract_inverted_index.offer | 156 |
| abstract_inverted_index.often | 5 |
| abstract_inverted_index.phase | 168 |
| abstract_inverted_index.these | 115 |
| abstract_inverted_index.those | 66 |
| abstract_inverted_index.which | 136 |
| abstract_inverted_index.(AQP4) | 82 |
| abstract_inverted_index.(Aβ), | 42 |
| abstract_inverted_index.causes | 139 |
| abstract_inverted_index.cortex | 59 |
| abstract_inverted_index.during | 142 |
| abstract_inverted_index.memory | 106 |
| abstract_inverted_index.neuron | 99 |
| abstract_inverted_index.normal | 68 |
| abstract_inverted_index.report | 24 |
| abstract_inverted_index.APP/PS1 | 32, 62, 112, 147 |
| abstract_inverted_index.cortex, | 135 |
| abstract_inverted_index.disease | 9 |
| abstract_inverted_index.evident | 54 |
| abstract_inverted_index.frontal | 57 |
| abstract_inverted_index.models, | 14 |
| abstract_inverted_index.neurons | 47 |
| abstract_inverted_index.remains | 20 |
| abstract_inverted_index.results | 116 |
| abstract_inverted_index.working | 105 |
| abstract_inverted_index.Deletion | 87 |
| abstract_inverted_index.although | 15 |
| abstract_inverted_index.analysis | 35 |
| abstract_inverted_index.compared | 64 |
| abstract_inverted_index.elusive. | 21 |
| abstract_inverted_index.mediated | 152 |
| abstract_inverted_index.neuronal | 130 |
| abstract_inverted_index.patients | 11 |
| abstract_inverted_index.revealed | 36 |
| abstract_inverted_index.strategy | 159 |
| abstract_inverted_index.symptoms | 4 |
| abstract_inverted_index.Moreover, | 70 |
| abstract_inverted_index.Together, | 114 |
| abstract_inverted_index.activity. | 69 |
| abstract_inverted_index.aquaporin | 80 |
| abstract_inverted_index.behaviors | 109 |
| abstract_inverted_index.clearance | 154 |
| abstract_inverted_index.improving | 150 |
| abstract_inverted_index.increased | 92, 125 |
| abstract_inverted_index.influence | 104 |
| abstract_inverted_index.locomotor | 140 |
| abstract_inverted_index.mechanism | 19 |
| abstract_inverted_index.phenotype | 73 |
| abstract_inverted_index.prodromal | 167 |
| abstract_inverted_index.transport | 85 |
| abstract_inverted_index.Therefore, | 149 |
| abstract_inverted_index.activation | 49 |
| abstract_inverted_index.amyloid-β | 41 |
| abstract_inverted_index.associated | 75 |
| abstract_inverted_index.astrocytes | 51 |
| abstract_inverted_index.behavioral | 1 |
| abstract_inverted_index.deficiency | 122 |
| abstract_inverted_index.expression | 44 |
| abstract_inverted_index.glymphatic | 84, 153 |
| abstract_inverted_index.4-month-old | 31, 111 |
| abstract_inverted_index.Alzheimer's | 8 |
| abstract_inverted_index.activation, | 100 |
| abstract_inverted_index.demonstrate | 117 |
| abstract_inverted_index.hyperactive | 61, 72 |
| abstract_inverted_index.impairment. | 86 |
| abstract_inverted_index.significant | 27 |
| abstract_inverted_index.variability | 29 |
| abstract_inverted_index.Pathological | 34 |
| abstract_inverted_index.accumulation | 39 |
| abstract_inverted_index.anxiety-like | 108 |
| abstract_inverted_index.intervention | 162 |
| abstract_inverted_index.perivascular | 79 |
| abstract_inverted_index.Non-cognitive | 0 |
| abstract_inverted_index.glutamatergic | 46, 98 |
| abstract_inverted_index.hyperactivity | 25, 131, 164 |
| abstract_inverted_index.intraneuronal | 38, 94, 126 |
| abstract_inverted_index.over-activity | 141 |
| abstract_inverted_index.psychological | 3 |
| abstract_inverted_index.hyperactivity, | 93 |
| abstract_inverted_index.mislocalization | 77, 120 |
| abstract_inverted_index.pathophysiology | 145 |
| abstract_inverted_index.inter-individual | 28 |
| abstract_inverted_index.neuropathological | 18 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 98 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 15 |
| citation_normalized_percentile.value | 0.95089776 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |