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Schizophrenia gene controls when new neurones mature

23 March 2009
Appeared in BioNews 500

Researchers at the Massachusetts Institute of Technology (MIT) Picower Institute for Learning and Memory in the US have found that a gene commonly associated with schizophrenia is essential for normal brain development and the growth of new neurons. The finding was reported in the journal Cell and could help lead to new treatments for the disorder, which affects up to one per cent of adults worldwide and is characterised by hallucinations, delusions, paranoia and depression.

The team, led by Li-Huei Tsai, the Picower Professor of Neuroscience, has shown for the first time that a gene known as DISC1 (disrupted in schizophrenia1) directly inhibits an enzyme called GSK3B (glycogen synthase kinase 3 beta). For decades doctors have treated bipolar disorder using lithium chloride treatments that target this enzyme.

The DISC1 gene was first identified in the 1990s when scientists studied a large Scottish family with mental disorders. They found that many of the family members who developed psychiatric disorders carried a mutation in the gene.

In a series of studies Tsai and colleagues found that DISC1 regulates the balance between neural stem cell self renewal and turning into neurons. A defective gene affects this balance and can lead to compromised cognition and behavioural abnormalities.

Tsai said: 'During brain development, a fine tuned mechanism regulates when neural stem cells divide and replenish their own population and when they turn into new neurons that will mature and grow appropriate connections with other neurons.'

The researchers found that the DISC1 gene is highly expressed in embryonic mice brain stem cells and also in the brain stem cells of adult mice. But when they inhibited the expression of DISC1, simulating what is occurring when someone carries a defective gene, it caused the stem cells to stop dividing and prematurely turn into newborn neurons.

In adult mice inhibition of DISC1 also produced behavioural side effects that were symptomatic of schizophrenia. For example the mice skittered around their cages, a behaviour which is often paralleled with mania in humans. These behavioural abnormalities were reversed when the DISC1 deficient mice were treated with a chemical inhibitor of GSK3B.

Tsai said that the findings are part of a larger picture of the genetic and developmental causes of psychological disorders. 'With this new knowledge of the DISC1-GSK3B interaction, one of the goals is to develop new drugs targeting schizophrenia, providing some hope that this devastating disease will be treated more effectively in the future,' she said.

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Schizophrenia-linked gene controls the birth of new neurons
EurekaAlert |  19 March 2009
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