Can mood stabilisers restore regular brain morphology?
Research has shown that the brains of patients with mental disorders contain abnormal formation of dendritic arbours, the 'landscape' of neurons linking to each other. The psychopathological mechanisms leading to irregular dendritic patterning are not completely understood, but recent research suggests this development may be due to changes in gene expression. If dendritic patterning can be controlled, it may be possible to effectively treat mental disorders. One school of thought is focusing on the misregulation of Sp4 transcription factor as the culprit behind the pathogenesis, as well as the possible therapeutic enabler. Transcription factors, such as Sp4, control when transcription — which is just one step in the process leading to gene expression — occurs, and how much genetic information is passed on. Sp4 is indicated in altered expression of genes that play a role in the pathogenesis as well as the therapy of neuropsychiatric disorders. The 'Transcriptional control of dendritic arbors morphology in pathogeny and therapy of neuropsychiatric diseases' (Psychiaprotegenomic) project aims to determine whether mood stabilisers and antipsychotic medication can reinstate normal dendritic patterning. The EU-funded project partners believe this can be done by stabilising or activating the Sp4 transcription factor. Studies are investigating whether the levels of Sp4 transcription factor protein or other factors are different in the post-mortem brain tissue of patients with affective disorders. The goal is to determine if such alterations lead to dendritic defects. Project partners have analysed Sp4 protein levels and Sp4 transcription factor in the tissue of schizophrenia (SCZ) patients. Comparisons have also been made with healthy subjects. As work continues, gene expression tests will be performed on post-mortem brains of neuropsychiatric patients to examine if changes in transcriptional regulation directly affect dendritic patterning. At the same time, researchers intend to study the effect of mood stabilisers and antipsychotics on dendritic morphology. In particular, they are interested to see if a lithium regime can change dendritic morphology through Sp4-dependent transcription regulation. The outcomes of Psychiaprotegenomic promise to enhance knowledge on how the regulation of Sp4 can be used to deal with the pathogenesis and therapy of mental disorders. Results will also give new insight into transcriptional programmes controlled by lithium.
