Immunoglobulins from motoneurone disease patients enhance glutamate release from rat hippocampal neurones in culture

Authors

  • Pavle R. Andjus,

    1. Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 2–4, 34014 Trieste, Italy.
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  • Zorica Stevic-Marinkovic,

    1. Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 2–4, 34014 Trieste, Italy.
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  • Enrico Cherubim

    Corresponding author
    1. Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), Via Beirut 2–4, 34014 Trieste, Italy.
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  • Authors' present addresses
    P. R. Andjus: Institute of Physiology and Biochemistry, School of Biology, University of Belgrade, Studentski trg 3, P.O.B. 52, 11000 Belgrade, FR Yugoslavia.

  • Authors' present addresses
    Z. Stevic-Marinkovic: Institute of Neurology, Clinical Centre of Serbia, University of Belgrade, 11000 Belgrade, FR Yugoslavia.

  • Author's email address
    E. Cherubini: cher@sissa.it

Abstract

  • 1The whole-cell configuration of the patch-clamp technique was used to study the effects of immunoglobulins (IgGs) from patients affected by amyotrophic lateral sclerosis (ALS) on spontaneous glutamatergic currents in rat hippocampal cells in culture.
  • 2Focal application of ALS IgGs (100 μg ml−1) to hippocampal cells induced a rise in frequency but not in amplitude of spontaneous excitatory postsynaptic currents (SEPSC) which outlasted the period of IgG application. The mean frequency ratio (ALS over control) was 3.2 ± 0.6 (n. 19). No changes in frequency or amplitude of SEPSCs were observed after treatment with IgGs obtained from healthy donors (n=5) or from patients with Alzheimer's disease (n=4).
  • 3ALS IgGs also increased the frequency (by a factor of 2.0 ± 0.3) but not the amplitude of miniature excitatory postsynaptic currents (mEPSC) recorded in the presence of TTX (n=19). A rise in frequency of mEPSC was also seen in cells superfused with a calcium-free solution (n=4).
  • 4In the presence of TTX, ALS IgGs did not modify the amplitude or the shape of currents evoked by AMPA (100 μm), recorded at a holding potential of −50 mV.
  • 5It is concluded that ALS IgGs enhance both SEPSCs and mEPSCs through a presynaptic type of action. The excessive release of glutamate from nerve endings may be the cause of motoneurone death in ALS patients.

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