Decrease in creatine kinase messenger RNA expression in the hippocampus and dorsolateral prefrontal cortex in bipolar disorder.

MacDonald ML, Naydenov A, Chu M, Matzilevich D, Konradi C
Bipolar Disord. 2006 8 (3): 255-64

PMID: 16696827 · PMCID: PMC4208624 · DOI:10.1111/j.1399-5618.2006.00302.x

OBJECTIVES - Bipolar disorder (BPD) affects more than 2 million adults in the USA and ranks among the top 10 causes of worldwide disabilities. Despite its prevalence, very little is known about the etiology of BPD. Recent evidence suggests that cellular energy metabolism is disturbed in BPD. Mitochondrial function is altered, and levels of high-energy phosphates, such as phosphocreatine (PCr), are reduced in the brain. This evidence has led to the hypothesis that deficiencies in energy metabolism could account for some of the pathophysiology observed in BPD. To further explore this hypothesis, we examined levels of creatine kinase (CK) mRNA, the enzyme involved in synthesis and metabolism of PCr, in the hippocampus (HIP) and dorsolateral prefrontal cortex (DLPFC) of control, BPD and schizophrenia subjects.

METHODS - Tissue was obtained from the Harvard Brain Tissue Resource Center. Real-time quantitative polymerase chain reaction (HIP, DLPFC) and gene expression microarrays (HIP) were employed to compare the brain and mitochondrial 1 isoforms of CK.

RESULTS - Both CK isoforms were downregulated in BPD. Furthermore, mRNA transcripts for oligodendrocyte-specific proteins were downregulated in the DLPFC, whereas the mRNA for the neuron-specific protein microtubule-associated protein 2 was downregulated in the HIP.

CONCLUSION - Although some of the downregulation of CK might be explained by cell loss, a more general mechanism seems to be responsible. The downregulation of CK transcripts, if translated into protein levels, could explain the reduction of high-energy phosphates previously observed in BPD.

MeSH Terms (19)

Adult Aged Animals Bipolar Disorder Creatine Kinase Female Gene Expression Regulation, Enzymologic Hippocampus Humans Male Middle Aged Mitochondria Phosphocreatine Polymerase Chain Reaction Prefrontal Cortex Protein Array Analysis Rats Rats, Sprague-Dawley RNA, Messenger

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