SP4 levels reduced in bipolar disorder patients
MedWire News: Results from a postmortem study indicate that individuals with bipolar disorder (BD) have reduced cerebellum and prefrontal cortex levels of the transcription factor specificity protein 4 (SP4).
The findings, published in the journal Bipolar Disorders, suggest that normalization of SP4 levels could be a potential strategy for treatment of the mood condition.
Belén Ramos (Centro de Investigación Biomédica en Red de Salud Mental [CIBERSAM], Barcelona, Spain) and colleagues explain that SP4, and the closely related factor SP1, regulate gene expression in a variety of biological processes, including neuronal development and function.
They add: "Human gene association studies and analysis of mutant mice suggest that… SP4 may be implicated in the pathophysiology of psychiatric diseases."
To investigate whether SP4 and SP1 levels are altered in the brains of BD patients, the team analyzed mRNA and protein levels of these factors in postmortem prefrontal cortex and cerebellum samples from 10 patients with the mood disorder and 10 mentally healthy controls who were matched for gender, age, and postmortem delay.
The researchers also investigated whether SP4 levels are regulated by neuronal activity and drug treatment in rat cerebellar granule neurons.
They found that SP4 and SP1 proteins, but not mRNA levels, were significantly reduced in the cerebellum of BD patients compared with controls.
Protein and mRNA levels of SP4, but not SP1, were also significantly reduced in the prefrontal cortex of BD patients compared with controls.
In rat neurons, they found that SP4, but not SP1, is rapidly degraded by enzymes in the absence of neuronal signalling (nondepolarized state), and that treatment with lithium stabilized and increased SP4 levels.
Ramos and team conclude: "Our study provides the first evidence of altered SP4 protein in the cerebellum and prefrontal cortex in BD subjects, supporting a possible role of transcription factor SP4 in the pathogenesis of the disease.
"In addition, our finding that SP4 stability is regulated by depolarization and lithium provides a pathway through which neuronal activity and lithium could control gene expression, suggesting that normalization of SP4 levels could contribute to treatment of affective disorders."
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By Mark Cowen