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

• Published in: Experimental brain research Vol. 225; no. 4; pp. 527 - 534
• Main Authors: Schaub, Christina, Uebachs, Mischa, Beck, Heinz, Linnebank, Michael
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2013; Springer; Springer Nature B.V
• Subjects: Action potential; Action Potentials - drug effects; Action Potentials - physiology; Alcohol; Alzheimer's disease; Analysis; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cell culture; Cognitive ability; Convulsions & seizures; Electrophysiology; Epilepsy; Evoked Potentials - drug effects; Evoked Potentials - physiology; Excitability; Fundamental and applied biological sciences. Psychology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus; Hippocampus (Brain); Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Homocysteine; Homocysteine - pharmacology; Homocystinuria; Inborn errors of metabolism; Isolated neuron and nerve. Neuroglia; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mental illness; Mental retardation; Metabolism; Mice; Nervous system; Nervous system (semeiology, syndromes); Neurodegeneration; Neurology; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Neurosciences; Neurotoxicity; Patch-Clamp Techniques; Physiological aspects; Plasma; Plasma levels; Research Article; Risk factors; Vascular diseases; Vertebrates: nervous system and sense organs; Germany; Homocysteine; Epilepsy; Excitability of neurons; Nervous system diseases; Rodentia; Central nervous system; Excitability; Metabolism; Long term; Encephalon; Cerebral disorder; Vertebrata; Mammalia; Neuron; Mouse; Central nervous system disease; Hippocampus
• ISSN: 0014-4819; 1432-1106
• DOI: 10.1007/s00221-012-3392-1

Homocystinuria is an inborn error of metabolism characterized by plasma homocysteine levels up to 500 μM, premature vascular events and mental retardation. Mild elevations of homocysteine plasma levels up to 25 μM, 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 (100 μM), or cell cultures were incubated with 100 μM homocysteine for 24 h. 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 (5 ms) were not altered by acute application or incubation of homocysteine. When we elicited trains of action potentials with prolonged current injections (200 ms), 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 24 h 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 24 h 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.