Abstract | BACKGROUND: METHODS: Rats received three injections of GAD65Ab b96.11 (5 or 7 μg), GAD65Ab b78 (5 or 7 μg), or saline at the level of three cerebellar nuclei. Animals were submitted to neurological evaluation and Morris Water Maze (MWM) test. Cellular internalization of GAD65Ab was analyzed by Flow Cytometry, Fluorescence and Bright Field microscopy. RESULTS: Monoclonal GAD65Ab induced dose-dependent and epitope-specific effects on motor and cognitive functions. Injections of the higher dose altered motor and spatial procedural behaviors, while the lower dose induced only modest cerebellar motor symptoms and did not affect MWM performances. While b96.11 provoked immediate severe effects, which rapidly decreased, b78 induced moderate but prolonged effects. Both GAD65Ab were taken up by live cells in a dose-dependent manner. CONCLUSIONS: Our findings support the hypothesis that epitope-specific GAD65Ab induce cerebellar dysfunction impairing motor and procedural abilities. This is the first demonstration of a critical role of cerebellar nuclei GAD65 enzyme in procedural spatial functions.
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Authors | Christiane S Hampe, Laura Petrosini, Paola De Bartolo, Paola Caporali, Debora Cutuli, Daniela Laricchiuta, Francesca Foti, Jared R Radtke, Veronika Vidova, Jérôme Honnorat, Mario Manto |
Journal | Orphanet journal of rare diseases
(Orphanet J Rare Dis)
Vol. 8
Pg. 82
(Jun 05 2013)
ISSN: 1750-1172 [Electronic] England |
PMID | 23738610
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Autoantibodies
- Epitopes
- Protein Isoforms
- Glutamate Decarboxylase
- glutamate decarboxylase 2
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Topics |
- Animals
- Antibodies, Monoclonal
(administration & dosage, immunology)
- Autoantibodies
- Behavior, Animal
(drug effects)
- Cell Line
- Cognition
(drug effects)
- Epitopes
(immunology)
- Glutamate Decarboxylase
(immunology)
- Male
- Motor Skills
(drug effects)
- Neurons
(drug effects)
- Protein Isoforms
(immunology)
- Rats
- Rats, Wistar
- Stiff-Person Syndrome
(immunology, physiopathology)
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