β-Amyloid Induces Local Neurite Degeneration in Cultured Hippocampal Neurons: Evidence for Neuritic Apoptosis
Open accessAbstract
Many apoptotic insults, including beta-amyloid, cause neuritic degeneration. The possibility that apoptotic insults act directly on neurites was investigated in experiments using compartmented cultures of hippocampal neurons. Neurites in modified Campenot chambers displayed morphological signs of degeneration, including beading or blebbing, when exposed to beta-amyloid. At short time points neurite degeneration was limited to the distal portions of neurites directly exposed to beta-amyloid. Furthermore, annexin V binding detected extracellular exposure of phosphatidylserine in portions of neurites directly exposed to apoptotic insults. Pretreatment of the cultures with zVAD-fmk blocked annexin V binding induced by beta-amyloid and concanavalin A, suggesting that caspase activity was required. Caspase activation was also visualized in neurites locally exposed to apoptotic insults. Together these results show that apoptotic insults cause local neurite degeneration which displays morphological and biochemical characteristics of apoptosis and suggest that neurite degeneration may use mechanisms common to apoptosis.
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Beading or blebbing in neurites is a marker of dystrophic neurites in the AD brain.
“Beading or blebbing in neurites is a marker of dystrophic neurites in the AD brain (3, 42, 43).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [42]
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- Authors
- Ivins, K. J., Bui, E. T. N., & Cotman, C. W.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Ivins, Kathryn J.
- ORCID
- Cotman, Carl W.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 1998-11
- Volume
- 5
- Issue
- 5
- Pages
- 365-378
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2012008959
- Cited by
- 164
- References
- 58
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 2 · 2014: 8 · 2013: 7 · 2012: 8
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5r01ag013007-05)
- University of California, Irvine
- National Institute on Aging (T32 AG00096, R01-AG13007)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, neurite degeneration, hippocampal neurons, phosphatidylserine exposure, annexin V binding, caspase activation, z-VAD-fmk, concanavalin A, Alzheimer's disease
- MeSH terms
- Animals, Cells, Cultured, Hippocampus, Nerve Degeneration, Neurons, Time Factors, Amyloid beta-Peptides, Neurites, Apoptosis, Annexin A5, Caspases, Rats
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