Aggravated effects of coexisting marginal thiamine deficits and zinc excess on SN56 neuronal cells

ABSTRACT

Objectives: Zinc excitotoxicity and thiamine pyrophosphate deficiency (TD) are known pathogenic signals contributing to mechanism of different encephalopathies through inhibition of enzymes responsible for energy metabolism such as pyruvate dehydrogenase, aconitase or ketoglutarate dehydrogenase. The aim of this work was to investigate whether subclinical Zn excess and TD, frequent in aging brain, may combine yielding overt neuronal impairment.

Results: Clonal SN56 cholinergic neuronal cells of septal origin were used as the model of brain cholinergic neurons, which are particularly susceptible to neurodegeneration in the course of Alzheimer’s disease, hypoxia and other dementia-linked brain pathologies. Neither subtoxic concentration of Zn (0.10 mM) nor mild 20–25% TD deficits alone caused significant negative changes in cultured cholinergic neurons viability and their acetyl-CoA/acetylcholine metabolism. However, cells with mild TD accumulated Zn in excess, which impaired their energy metabolism causing a loss of neurons viability and their function as neurotransmitters. These negative effects of Zn were aggravated by amprolium which is an inhibitor of thiamine intracellular transport.

Conclusion: Our data indicate that TD may amplify otherwise non-harmful border-line Zn excitotoxic signals yielding progress of neurodegeneration.

KEYWORDS:

• Thiamine deficiency
• zinc neurotoxicity
• cholinergic neurons
• acetyl-CoA
• energy metabolism
• Alzheimer disease
• pyruvate dehydrogenase
• SN56 cells

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is supported by the Polish Ministry of Research and Higher Education for Medical University of Gdansk fund St57 (MN001-0059/08 and MN 01-0171/08/248).

Notes on contributors

Anna Ronowska

Anna Ronowska, Ph.D. is a lecturer (specialist in enzymology) at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland, since 2008.

Sylwia Gul-Hinc

Sylwia Gul-Hinc, Ph.D. is a lecturer (specialist in neuronal biology) at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland, since 2012.

Anna Michno

Anna Michno, Ph.D. is a lecturer (specialist in cellular metabolism) at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland, since 2007.

Dorota Bizon-Zygmańska

Dorota Bizon-Zygmańska, Ph.D. is a lecturer (specialist in enzymology) at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland, since 1992.

Marlena Zyśk

Marlena Zyśk, Ph.D. is a lecturer (specialist in molecular biology) at the Department of Molecular Medicine, Medical University of Gdansk, Gdansk, Poland, since 2013.

Hanna Bielarczyk

Hanna Bielarczyk is professor at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland. The author of widely used estimation of acetyl-CoA.

Andrzej Szutowicz

Andrzej Szutowicz is professor (specialist in neuroscience) at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland.

Beata Gapys

Beata Gapys is Master of Science at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland, Beata Gapys.

Agnieszka Jankowska-Kulawy

Agnieszka Jankowska-Kulawy is at the Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland.