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Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia
Open accessAbstract
ABSTRACT Progranulin haploinsufficiency causes frontotemporal dementia with tau‐negative, ubiq‐uitin‐positive neuronal inclusion pathology. In this study, we showed that progranulin‐deficient mice displayed increased depression‐ and disinhibition‐like behavior, as well as deficits in social recognition from a relatively young age. These mice did not have any deficit in locomotion or exploration. Eighteen‐month‐old progranulin‐deficient mice demonstrated impaired spatial learning and memory in the Morris water maze. In addition to behavioral deficits, progranulin‐deficient mice showed a progressive development of neuropathology from 12 mo of age, including enhanced activation of microglia and astro‐cytes and ubiquitination and cytoplasmic accumulation of phosphorylated TDP‐43. Thus, progranulin deficiency induced FTD‐like behavioral and neuro‐pathological deficits. These mice may serve as an important tool for deciphering underlying mechanisms in frontotemporal dementia.—Yin, F., Du‐mont, M., Banerjee, R., Ma, Y., Li, H., Lin, M. T., Beal, M. F., Nathan, C., Thomas, B., Ding, A. Behavioral deficits and progressive neuropathology in progranulin‐deficient mice: a mouse model of frontotemporal dementia. FASEB J. 24, 4639–4647 (2010). www.fasebj.org
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“This is in line with findings which have shown that lipid droplet containing immune cells in the periphery are detrimental, including foamy macrophages in atherosclerosis10 or lipid droplet-rich eosinophils in experimental models of allergy37.”
From Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (2020) · cites this paper as [37]
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Metadata
- Authors
- Yin, F., Dumont, M., Banerjee, R., Ma, Y., Li, H., Lin, M. T., Beal, M. F., Nathan, C., Thomas, B., & Ding, A.
- Affiliations
- Cornell University (US)
- Weill Cornell Medicine (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-12
- Volume
- 24
- Issue
- 12
- Pages
- 4639-4647
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC2992364
- OpenAlex
- W2106248056
- Cited by
- 180
- References
- 30
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 11 · 2022: 4 · 2021: 12 · 2020: 12 · 2019: 10 · 2018: 17 · 2017: 20 · 2016: 14 · 2015: 15 · 2014: 12 · 2013: 8 · 2012: 13
- FWCI
- 7.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The FASEB Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM061710, AI030165)
- National Institute on Aging (R01AG020729)
- National Institute of General Medical Sciences (R01GM061710, GM061710)
- National Institute of Allergy and Infectious Diseases (AI030165, R01AI030165)
- National Institute of Neurological Disorders and Stroke (R01NS060885, NS060885, NS062165, R21NS062165)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- progranulin, frontotemporal dementia, haploinsufficiency, behavioral deficits, depression-like behavior, social recognition, spatial learning and memory, microglial activation, astrocyte activation, ubiquitination, TDP-43 phosphorylation, neuropathology, mouse model
- MeSH terms
- Progranulins, Granulins, Animals, Disease Models, Animal, DNA-Binding Proteins, Immunohistochemistry, Maze Learning, Intercellular Signaling Peptides and Proteins, Mice, Frontotemporal Dementia
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