RESUMO
BACKGROUND: Evidence supports the role for mitochondrial impairment in the pathophysiology of bipolar disorder (BD). BD has been associated with decreased mitochondrial electron transport chain activity and increased oxidative stress. Also, mitochondrial DNA (mtDNA) encodes mitochondrial electron transport chain proteins and has been associated with altered oxidative stress. Preclinical studies showed that lithium treatment increased mtDNA content, but no study has directly assessed mtDNA content in subjects with BD in vivo. Also, the effects of lithium treatment on mtDNA content have never been evaluated in humans. METHODS: Leukocyte mtDNA content using real time-PCR was evaluated in subjects with BD (n=23) in a depressive episode (≥18 in the 21-item Hamilton Depression Rating Scale) before and after 6-week lithium treatment versus healthy controls (n=24). RESULTS: mtDNA content showed no significant difference between subjects with BD at baseline and controls (p=0.46); also no difference was observed when comparing before and after lithium treatment. A trend for decreased mtDNA content was specifically observed in BD type I compared to controls and BD type II (p=0.05). Importantly, endpoint mtDNA copy number was significantly correlated with age. CONCLUSION: In BD subjects who were younger, unmedicated and had a shorter duration of illness, no change was observed in mtDNA copy number. More studies with larger samples are warranted to evaluate mtDNA content changes in BD and its potential role as a treatment target, especially in BD type I and its association with aging.
Assuntos
Transtorno Bipolar/sangue , Transtorno Bipolar/genética , Variações do Número de Cópias de DNA/genética , DNA Mitocondrial/genética , Leucócitos/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The ADAMs comprises a family of cell surface proteins with putative roles in cell-cell and/or cell-matrix interactions and in protease activities. In this work, we have examined the expression level and the methylation status of the 5' upstream region of the adhesion molecule ADAM23 in two brain tumor cell lines (A172 and T98G) as well as in three primary brain tumors (one grade II astrocytoma and two meningiomas) and 15 glioblastoma xenografts. Using bisulfite sequencing we verified that the percentage of methylated dinucleotides is higher in T98G when compared to A172 and that methylation significantly correlates with ADAM23 mRNA and protein expression. However, we were unable to detect methylation and down-regulation of the ADAM23 gene in brain tumors. Together, these results indicate that ADAM23 down-regulation by methylation in brain tumors is a rare event and it may help explain why brain tumor metastases are rarely found elsewhere in the body.