Cited by 33Prion Diseases and Protein MisfoldingNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

Loss of Perineuronal Net in ME7 Prion Disease

Franklin, Sarah L., Love, Seth, Greene, J. Richard T., Betmouni, Samar·2008·Journal of Neuropathology & Experimental Neurology

Abstract

Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid [GABA]) inhibitory interneurons, we investigated the temporal relationships between microglial activation and loss of PN and PV-positive neurons in ME7 murine prion disease. Anesthetized C57Bl/6J mice received bilateral intracerebral microinjections of ME7-infected or normal brain homogenate into the dorsal hippocampus. Microglial activation, PrP accumulation, the number of PV-positive interneurons, and Wisteria floribunda agglutinin-positive neurons (i.e. those with an intact PN) were assessed in the ventral CA1 and subiculum at 4, 8, 12, 16, and 20 weeks postinjection. Hippocampal areas and total neuron numbers in the ventral CA1 and subiculum were also determined. Loss of PN coincided with early microglial activation and with a reduction in synaptic plasticity. No significant loss of PV-positive interneurons was observed. Our findings suggest that the substrate of the earliest synaptic and behavioral abnormalities in murine prion disease may be inflammatory microglia-mediated degradation of the PN.

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Crossref · 10.1097/nen.0b013e3181654386

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Authors
Franklin, S. L., Love, S., Greene, J. R. T., & Betmouni, S.
Affiliations
North Bristol NHS Trust (GB)
Corresponding author
Betmouni, Samar
Venue
Journal of Neuropathology & Experimental Neurology
Published
2008-03
Volume
67
Issue
3
Pages
189-199
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
OpenAlex
W1969768014
Cited by
33
References
42
Citations by year
2025: 3 · 2024: 3 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 1 · 2012: 5
FWCI
0.41
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion)
  • Bradford Scholars (University of Bradford) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
perineuronal nets, microglial activation, parvalbumin interneurons, synaptic plasticity, hippocampus, ventral CA1, subiculum, Wisteria floribunda agglutinin, extracellular matrix degradation, prion protein accumulation, neuroinflammation, GABAergic interneurons
MeSH terms
Animals, Disease Models, Animal, Encephalitis, Extracellular Matrix, Female, gamma-Aminobutyric Acid, Gliosis, Hippocampus, Interneurons, Mice, Inbred C57BL, Nerve Degeneration, Neural Pathways, Neuronal Plasticity, Parvalbumins, Staining and Labeling, Prion Diseases, Microglia, Disease Progression, PrPSc Proteins, Receptors, N-Acetylglucosamine, Plant Lectins, Mice

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