Thiamine deficiency during pregnancy leads to cerebellar neuronal death in rat offspring: role of voltage-dependent K+ channels.
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.
Oliveira
Fernando Augusto
FA
Departamento de Bioquimica e Imunologia, Universidade Federal de Minas Gerais, Avenida Antonio Carlos, #6627, Instituto de Ciências Biológicas, Bloco K4, Sala #167, Belo Horizonte-MG, Brazil.
Galan
Diogo Teodoro
DT
Ribeiro
Angela Maria
AM
Santos Cruz
Jader
J
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D048070:Fetal Nutrition Disorders / Q000378:metabolism* / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013132:Spinocerebellar Degenerations / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013831:Thiamine / Q000378:metabolism; D013832:Thiamine Deficiency / Q000150:complications* / Q000503:physiopathology
D024642:Potassium Channels, Voltage-Gated; D013831:Thiamine