Role-playing Gene in Schizophrenia is Involved in More Brain Processes Than Previously Thought

Author:  Falishia Sloan
Institution:  Eastern Virginia Medical School
Date:  September 2007

In a study published online by Cell, a publication of Cell Press, scientists have found that a gene known to have a significant part in the neurological disorder known as schizophrenia also has a greater role in the brain than previously thought. The newly discovered aspects of the gene, known as Disrupted-In-Schizophrenia 1 (DISC1), could lead to better explanations of the development and observed prognosis of schizophrenia.

Schizophrenia is a psychiatric brain disease in which patients may experience visual or auditory hallucinations or an unrealistic view of reality. Symptoms commonly are known to begin in patients around adolescence. An increase in activity related to dopamine, a neurohormone released by the hypothalamus, is known to be a key feature of schizophrenia.

In the current research, the scientists found that newborn neurons sans the DISC1 gene propagated neuronal signals have an increased excitability and developed more synapses between neurons than other brain cells. Using mice, the research team also found an increased rate of incorporation of new neurons into existing brain cells in mice with just a few DISC1-reduced brain cells. Irregularly shaped neurons resulted from the confused activity and ended up being positioned irregularly, as well. From their research, the scientists were able to deduce that DISC1 plays a role in incorporating and controlling new neurons into the adult brain.

Study collaborator Bai Lu of the National Institute of Mental Health, stated, "This study reveals two unexpected functions of DISC1 [in the adult brain]: regulation of synapse formation and neuronal firing." Furthermore, according to Dr. Lu, the dysfunction of these activities has been linked to the development of schizophrenia.

Hongjun Song of Johns Hopkins stated, "Normally, new neurons migrate within certain ranges, but cells with reduced DISC1 overshoot and end up in the wrong place. They also grow a lot more dendritic processes and fire at a faster rate. Synapse formation is much faster. A series of things go wrong, and everything is sped up. It appears that they just can't stop somehow."

In the current study, the researchers studied what the DISC1 gene does in live animals by manipulating DISC1 activity in the hippocampuses of individual neural stem cells of adult mice. According to Dr. Lu, "It appears that you need tight regulation of DISC1 levels for new neurons to integrate into the brain circuitry properly,"

"In vivo, DISC1 does more than expected, regulating many processes essential for establishing a network for brain function. We were also surprised to find that the gene does something different in the adult brain than what it seems to do in embryonic stages," stated Dr. Song.

According to Dr. Lu, abnormal adult brain function may result from abnormal function of neuronal circuitry that comes from a decrease in the levels of DISC1 during development. In addition to schizophrenia, mutations in the gene encoding DISC1 have been linked with various other mood disorders and conditions in multiple family pedigrees.

Author: Falishia Sloan

Reviewed by: Pooja Ghatalia

Published by: Konrad Sawicki