Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies

Ann Neurol. 2003 Mar;53(3):325-36. doi: 10.1002/ana.10451.


Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1-Abs block induction of long-term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Autoantibodies / adverse effects*
  • Autoantibodies / blood
  • Autoantibodies / pharmacology
  • Cells, Cultured
  • Cerebellar Diseases / immunology*
  • Cerebellar Diseases / pathology*
  • Cerebellar Diseases / physiopathology
  • Female
  • Hodgkin Disease / blood
  • Hodgkin Disease / pathology
  • Hodgkin Disease / physiopathology
  • Humans
  • Long-Term Synaptic Depression / drug effects
  • Long-Term Synaptic Depression / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Motor Skills / drug effects
  • Motor Skills / physiology
  • Paraneoplastic Cerebellar Degeneration / pathology
  • Paraneoplastic Cerebellar Degeneration / physiopathology
  • Purkinje Cells / drug effects
  • Purkinje Cells / pathology
  • Purkinje Cells / physiology
  • Receptors, Metabotropic Glutamate / blood
  • Receptors, Metabotropic Glutamate / immunology*
  • Saccades / physiology


  • Autoantibodies
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1