English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  Stiff Person Syndrome (SPS) is a rare autoimmune movement disorder characterized by the presence of autoantibodies specific to the smaller isoform of glutamate decarboxylase (GAD65). A pathological role of these antibodies has been suggested by their capacity to inhibit GAD65 enzyme activity and by the observation that rats receiving cerebellar injections of GAD65Ab showed cerebellar motor hyperexcitability. To assess the effect of epitope-specific GAD65Ab on cognitive and motor functions, we conducted behavioral experiments in rats that received cerebellar injections with two distinct monoclonal GAD65Ab (b96.11 and b78).    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.

Monoclonal antibodies to 65kDa glutamate decarboxylase induce epitope specific effects on motor and cognitive functions in rats