Loss of Perineuronal Net in ME7 Prion Disease
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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Perineuronal net loss is reported in seizure and prion disease.
“PNN loss is also reported in other neurological disorders such as seizure [34] and prion disease [35]”
From Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain (2020) · cites this paper as [35]
Microglia are postulated to degrade PNNs in some disease states, probably via increased extracellular proteases.
“it has been postulated that microglia mediate the degradation of PNNs in certain disease states, likely through enhanced production of extracellular proteases”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Franklin et al., 2008
Stress and immune responses markedly affect PNN integrity and metalloprotease expression.
“Second, PNN integrity and expression of metalloproteases are markedly affected by stress and immune responses (Fillman et al., 2014; Franklin et al., 2008; Gray et al., 2008; Medina-Flores et al., 2004).”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Franklin et al., 2008
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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
- Publisher
- Oxford University Press (OUP)
- 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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