Presymptomatically applied AMPA receptor antagonist prevents calcium increase in vulnerable type of motor axon terminals of mice modeling amyotrophic lateral sclerosis

Roland Patai, Melinda Paizs, Massimo Tortarolo, Caterina Bendotti, Izabella Obál, József I. Engelhardt, László Siklós

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Increased intracellular calcium (Ca), which might be the consequence of an excess influx through Ca-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, plays a crucial role in degeneration of motor neurons. Previously we demonstrated that the presymptomatic application of AMPA receptor antagonist, talampanel, could reduce Ca elevation in spinal motor neurons of mice carrying the G93A mutation of superoxide dismutase 1 (SOD1), modeling amyotrophic lateral sclerosis (ALS). It remained to be examined whether the remote, functionally semi-autonomous motor axon terminals could be rescued from the Ca overload, or if the terminals, where the degeneration possibly starts, already experience intractable changes at early time points. Thus using electron microscopic techniques, we measured the Ca level of motor axon terminals in the interosseus muscle of the SOD1 mutant animals, which are prototypes of vulnerable nerve endings in ALS. In line with the results obtained in the perikarya, talampanel treatment could reduce Ca increase evoked by the presence of mutant SOD1 in the axon terminals if the treatment was started presymptomatically but not at an early symptomatic stage. We also tested the Ca level in the cell bodies and axon terminals of the oculomotor neurons, which are resistant to the disease. Neither Ca increase, nor talampanel effect could be demonstrated at either time point. This is consistent with the observations that oculomotor neurons contain increased level of Ca buffer, which could reduce excess Ca load, and they also express glutamate receptor subunit type 2, which renders AMPA receptors impermeable to Ca.

Original languageEnglish
Pages (from-to)1739-1748
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1863
Issue number7
DOIs
Publication statusPublished - Jul 2017

Keywords

  • AMPA receptor antagonist
  • Amyotrophic lateral sclerosis
  • Electron microscopy
  • Intracellular calcium
  • Talampanel

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Fingerprint Dive into the research topics of 'Presymptomatically applied AMPA receptor antagonist prevents calcium increase in vulnerable type of motor axon terminals of mice modeling amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

  • Cite this