Late onset neurodegeneration in the Cln3−/− mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation

Autor: Jonathan D. Cooper, Nisha Parihar, Hannah M. Mitchison, Payam Rezaie, William C. Mobley, David A. Pearce, Shubhodeep Chakrabarti, Charlie C. Pontikis, Ming K. Lim, Claire V. Cella
Rok vydání: 2004
Předmět:
Calbindins
Pathology
Cell Count
Mice
Gliosis
Mice
Knockout
CD11b Antigen
Membrane Glycoproteins
Neocortex
General Neuroscience
Neurodegeneration
Age Factors
Brain
Immunohistochemistry
Parvalbumins
medicine.anatomical_structure
Knockout mouse
Neuroglia
Somatostatin
medicine.medical_specialty
Batten disease
Interneuron
Cell Survival
Antigens
Differentiation
Myelomonocytic
Mice
Inbred Strains
Biology
Statistics
Nonparametric
S100 Calcium Binding Protein G
Atrophy
Antigens
CD
Interneurons
Neuronal Ceroid-Lipofuscinoses
Glial Fibrillary Acidic Protein
medicine
Animals
Molecular Biology
Cell Size
Staining and Labeling
medicine.disease
Antigens
Differentiation
Disease Models
Animal
nervous system
Astrocytes
Nerve Degeneration
Neuronal ceroid lipofuscinosis
Neurology (clinical)
Neuroscience
Molecular Chaperones
Developmental Biology
Zdroj: Brain Research. 1023:231-242
ISSN: 0006-8993
DOI: 10.1016/j.brainres.2004.07.030
Popis: Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.
Databáze: OpenAIRE
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