Core features of frontotemporal dementia recapitulated in progranulin knockout mice
Open accessAbstract
Frontotemporal dementia (FTD) is typified by behavioral and cognitive changes manifested as altered social comportment and impaired memory performance. To investigate the neurodegenerative consequences of progranulin gene (GRN) mutations, which cause an inherited form of FTD, we used previously generated progranulin knockout mice (Grn-/-). Specifically, we characterized two cohorts of early and later middle-aged wild type and knockout mice using a battery of tests to assess neurological integrity and behavioral phenotypes analogous to FTD. The Grn-/- mice exhibited reduced social engagement and learning and memory deficits. Immunohistochemical approaches were used to demonstrate the presence of lesions characteristic of frontotemporal lobar degeneration (FTLD) with GRN mutation including ubiquitination, microgliosis, and reactive astrocytosis, the pathological substrate of FTD. Importantly, Grn-/- mice also have decreased overall survival compared to Grn+/+ mice. These data suggest that the Grn-/- mouse reproduces some core features of FTD with respect to behavior, pathology, and survival. This murine model may serve as a valuable in vivo model of FTLD with GRN mutation through which molecular mechanisms underlying the disease can be further dissected.
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Metabolic changes towards increased fatty acid production cause lipid droplet formation in immune cells and cancer cells.
“Besides inflammation, metabolic changes towards increased fatty acid production have been reported to cause lipid droplet formation in immune cells9 and also in cancer cells41.”
From Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (2020) · cites this paper as [41]
The Results section on microglial activation reports increased microglia/macrophages in progranulin-knockout mice, and the ubiquitin-immunoreactivity section mentions a few foamy macrophages. Neither passage addresses increased fatty acid production or lipid droplet formation in immune cells. Searches for those terms found no supporting passage; the cancer-cell portion is attached to a different citation. (LLM, conf=0.75)
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- Authors
- Ghoshal, N., Dearborn, J. T., Wozniak, D. F., & Cairns, N. J.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Ghoshal, N.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 45
- Issue
- 1
- Pages
- 395-408
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC3225509
- OpenAlex
- W2084343282
- Cited by
- 127
- References
- 4
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 15 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 11 · 2017: 13 · 2016: 8 · 2015: 10 · 2014: 8 · 2013: 8 · 2012: 13
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (P01-AG003991, T32-NS007205, P50-AG005681, P30-NS057105)
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- frontotemporal dementia, progranulin, frontotemporal lobar degeneration, social behavior deficits, learning and memory impairment, ubiquitination, microglial activation, reactive astrogliosis, survival, animal models of neurodegeneration
- MeSH terms
- Progranulins, Granulins, Animals, Behavior, Animal, Brain, Cell Count, Disease Models, Animal, Exploratory Behavior, Male, Motor Activity, Neurons, Mice, Knockout, Maze Learning, Intercellular Signaling Peptides and Proteins, Mice, Frontotemporal Dementia
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