Cited by 244Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Release of amyloid beta-protein precursor derivatives by electrical depolarization of rat hippocampal slices

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Nitsch, R M, Farber, S A, Growdon, J H, Wurtman, R J·1993·Proceedings of the National Academy of Sciences

Abstract

Proteolytic processing of the beta-amyloid protein precursor (APP) is regulated by cell-surface receptors. To determine whether neurotransmitter release in response to neuronal activation regulates APP processing in brain, we electrically depolarized superfused rat hippocampal slices and measured soluble APP derivatives released into the superfusate. Electrical depolarization caused a rapid increase in the release of both neurotransmitters and amino-terminal APP cleavage products. These derivatives lacked the APP carboxyl terminus and were similar to those found in both cell culture media and human cerebrospinal fluid. Superfusate proteins including lactate dehydrogenase were not changed by electrical depolarization. The release of amino-terminal APP derivatives increased with increasing stimulation frequencies from 0 to 30 Hz. The increased release was inhibited by the sodium-channel antagonist tetrodotoxin, suggesting that action-potential formation mediates the release of large amino-terminal APP derivatives. These results suggest that neuronal activity regulates APP processing in the mammalian brain.

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Crossref · 10.1073/pnas.90.11.5191

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Authors
Nitsch, R. M., Farber, S. A., Growdon, J. H., & Wurtman, R. J.
Affiliations
Massachusetts Institute of Technology (US)
Venue
Proceedings of the National Academy of Sciences
Published
1993-06
Volume
90
Issue
11
Pages
5191-5193
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2046948924
Cited by
244
References
20
Citations by year
2026: 3 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 4 · 2019: 9 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 3
FWCI
11.11
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid precursor protein, APP processing, hippocampal slices, neurotransmitter release, tetrodotoxin, sodium channels, action potential, neuronal activity regulation, cerebrospinal fluid, lactate dehydrogenase
MeSH terms
Acetylcholine, Animals, Electric Stimulation, Hippocampus, L-Lactate Dehydrogenase, Male, Perfusion, Tetrodotoxin, Immunoblotting, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Rats, In Vitro Techniques

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