Thiamine deficiency during pregnancy leads to cerebellar neuronal death in rat offspring: role of voltage-dependent K+ channels

Brain Res. 2007 Feb 23;1134(1):79-86. doi: 10.1016/j.brainres.2006.11.064. Epub 2007 Jan 2.

Abstract

Oxidative stress, selective neuronal loss, and diminished activity of thiamine-dependent enzymes play a role in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. To further understand the major implications of thiamine deficiency (TD) in neuronal death, we induced TD during pregnancy and evaluated the effects on the offspring. The body and brain weights of pups from thiamine-deficient dams were significantly smaller than normal. Loss of neuronal viability was examined by trypan blue exclusion assay, and demonstrated increased cytotoxicity in primary cultures of TD neurons. Additionally, cerebellar cultures were exposed to thiamine-free cell culture medium to better explore the effects of thiamine withdrawal. Alterations in potassium current has previously been associated with the development of cell death. In this study, we examined the TD effects on delayed rectifier and A-type K+ channels, two well-known voltage-activated K+ channels involved in the regulation of action potential firing in cerebellar granule neurons. Current recordings were performed in cultured rat cerebellar granule neurons at day 7, using the whole-cell voltage-clamp technique. Our data demonstrate that thiamine deficiency provoked a significant decrease in the voltage-dependent K+ membrane conductance. Finally, TD markedly depressed the transient A-type K+ currents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / physiology
  • Cells, Cultured
  • Cerebellum / abnormalities*
  • Cerebellum / metabolism
  • Cerebellum / physiopathology
  • Female
  • Fetal Nutrition Disorders / metabolism*
  • Fetal Nutrition Disorders / physiopathology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Nerve Degeneration / etiology
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / physiopathology
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidative Stress / physiology
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / metabolism*
  • Pregnancy
  • Pregnancy Complications / metabolism
  • Pregnancy Complications / physiopathology
  • Rats
  • Rats, Wistar
  • Spinocerebellar Degenerations / etiology
  • Spinocerebellar Degenerations / metabolism*
  • Spinocerebellar Degenerations / physiopathology
  • Thiamine / metabolism
  • Thiamine Deficiency / complications*
  • Thiamine Deficiency / physiopathology

Substances

  • Potassium Channels, Voltage-Gated
  • Thiamine