Fulltext

Chronic homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons

Schaub, Christina ; Uebachs, Mischa ; Beck, Heinz ; Linnebank, Michael

In: Experimental Brain Research, 2013, vol. 225, no. 4, p. 527-534

Add to personal list
    Title
    • Chronic homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons
    Author
    • Schaub, Christina. Department of Neurology, University of Bonn, Bonn, Germany
    • Uebachs, Mischa. Department of Neurology, University of Bonn, Bonn, Germany
    • Beck, Heinz. Department of Epileptology, University of Bonn, Bonn, Germany
    • Linnebank, Michael. Department of Neurology, University of Bonn, Bonn, Germany
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:321026
    Summary
    Homocystinuria is an inborn error of metabolism characterized by plasma homocysteine levels up to 500μM, premature vascular events and mental retardation. Mild elevations of homocysteine plasma levels up to 25μM, which are common in the general population, are associated with vascular disease, cognitive impairment and neurodegeneration. Several mechanisms of homocysteine neurotoxicity have been investigated. However, information on putative effects of hyperhomocysteinemia on the electrophysiology of neurons is limited. To screen for such effects, we examined primary cultures of mouse hippocampal neurons with the whole-cell patch-clamp technique. Homocysteine was applied intracellularly (100μM), or cell cultures were incubated with 100μM homocysteine for 24h. Membrane voltage was measured in current-clamp mode, and action potential firing was induced with short and prolonged current injections. Single action potentials induced by short current injections (5ms) were not altered by acute application or incubation of homocysteine. When we elicited trains of action potentials with prolonged current injections (200ms), a broadening of action potentials during repetitive firing was observed in control neurons. This spike broadening was unaltered by acute application of homocysteine. However, it was significantly diminished when incubation with homocysteine was extended to 24h prior to recording. Furthermore, the number of action potentials elicited by low current injections was reduced after long-term incubation with homocysteine, but not by the acute application. After 24h of homocysteine incubation, the input resistance was reduced which might have contributed to the observed alterations in membrane excitability. We conclude that homocysteine exposure causes changes in the intrinsic electrophysiological properties of cultured hippocampal neurons as a mechanism of neurological symptoms of hyperhomocysteinemia