Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

R. H. Olesen, Thomas Hyde, Joel Kleinman, K. Smidt, J. Rungby, A. Larsen

Research output: Contribution to journalArticle

Abstract

The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)e838
JournalTranslational Psychiatry
Volume6
Issue number6
DOIs
StatePublished - Jun 14 2016
Externally publishedYes

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Zinc
Obesity
Gene Expression
Brain
Alzheimer Disease
Proteins
Body Mass Index
Frontal Lobe
Homeostasis
Synaptic Vesicles
zinc-binding protein
N-Methyl-D-Aspartate Receptors
Neurodegenerative Diseases
African Americans
Dementia
Glutamic Acid
Apoptosis
Incidence
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain. / Olesen, R. H.; Hyde, Thomas; Kleinman, Joel; Smidt, K.; Rungby, J.; Larsen, A.

In: Translational Psychiatry, Vol. 6, No. 6, 14.06.2016, p. e838.

Research output: Contribution to journalArticle

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