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


CONCLUSIONS
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.
MacDonald
Matthew L
ML
Laboratory of Neuroplasticity, McLean Hospital, Belmont, MA 02478, USA.
Naydenov
Alipi
A
Chu
Melissa
M
Matzilevich
David
D
Konradi
Christine
C
D000328:Adult; D000368:Aged; D000818:Animals; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D003402:Creatine Kinase / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006624:Hippocampus / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017397:Prefrontal Cortex / Q000033:anatomy & histology* / Q000201:enzymology*; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D010725:Phosphocreatine; D003402:Creatine Kinase