Ramos explained that SP4 belongs to a category of proteins known as transcription factors, which regulate gene expression. "While this study examined the SP4 protein levels, mutations in the gene encoding the SP4 protein have been associated with psychiatric diseases including bipolar disorder, a poorly understood disease characterized by episodes of abnormally elevated energy levels with or without depressive episodes, as well as schizophrenia, and major depressive disorder. Thus, our study adds to the growing body of evidence that alterations in gene regulation contribute to the development of psychiatric disorders," said Ramos.
Further analysis showed that SP4 levels are regulated by neuronal activity, indicating that this transcription factor is important for normal neuronal signaling. "Looking at normal rat neurons in culture, we found that SP4 is rapidly degraded by enzymes in the absence of neuronal signaling, which we refer to as the non-depolarized state," said first author Raquel Pinacho, BS, MS, a graduate student in Ramos' lab in PSSJD.
In previous work, the researchers had identified an essential role for SP4 in regulating the structure of nerve cells during development. Taken together, the findings suggest that reduced levels of this protein may contribute to altered patterns of nerve cells in the brain.
"Moreover," added Ramos, "we demonstrated that the destruction of SP4 by enzymes was inhibited by lithium, a drug widely used as a mood stabilizer for patients with bipolar disorder. When lithium was added to cells in the non-depolarized -- inactive -- state, levels of SP4 were stabilized and increased. This finding suggests that the therapeutic effects of lithium may be related, at least in part, to changes in gene expression leading to changes in cellular structure and fu
|Contact: Siobhan E. Gallagher|
Tufts University, Health Sciences Campus