Research led by scientists from Duke-NUS Graduate Medical School Singapore (Duke-NUS) has linked the abnormal behaviour of two genes (BDNF and DTNBP1) to the underlying cause of schizophrenia. These findings have provided a new target for schizophrenia treatment.
facts at a glance:
The study was published online in the journal Biological Psychiatry.
DTNBP1 and BDNF are two genes that increase the risk of schizophrenia.
Dr. Je’s study is the first ever to show that DTNBP1 is required for proper trafficking of BDNF to its appropriate location within the brain circuit.
BDNF is required for the development and action of interneurons within the brain circuit that maintains signalling balance.
Results have shown that regulating BDNF levels can rescue the signalling imbalance observed in schizophrenia, providing new hope for a treatment.
“We wanted to understand the mechanism by which the brain circuit operates,” explained senior author Assistant Professor Shawn Je, from the Neuroscience and Behavioural Disorders Programme at Duke-NUS. “In particular, we wanted to understand the ability of a specific type of cell in the brain, termed interneurons, to modulate brain network activity to maintain a balance in brain signalling.”
Dr. Je and his team analysed signalling activity in neuronal cultures that either did not have the DTNBP1 gene or had lowered levels of the gene, because reduced DTNBP1 levels and genetic disruptions of DTNBP1 in mice resulted in schizophrenia-like behaviours. Using multiple model systems, they found that the low levels of DTNBP1 resulted in dysfunctional interneurons and over-activated neuronal network activity. Reducing levels of DTNBP1 also lowered the levels of the secreted protein molecule, BDNF.
Read the full story here:
Regulation of Brain-Derived Neurotrophic Factor Exocytosis and Gamma-Aminobutyric Acidergic Interneuron Synapse by the Schizophrenia Susceptibility Gene Dysbindin-1