A Research Blog

Zika - the earthly virus

An image of the Zika virus particle structure, derived from a cryo-electron microscopy technique.
The structure is coloured to resemble Earth while the region of South America, which is heavily affected by the Zika virus, is highlighted in red.

Image by Dr Guntur Fibriansah, Senior Research Fellow in the Emerging Infectious Diseases Programme
Duke-NUS Medical School

Events at synaptic terminal underlying glutamate releaseFirst steps taken in understanding psychiatric disorders

A team from Duke-NUS Medical School and the National University of Singapore discovered how a major susceptibility gene for mental illness – Disrupted-In-Schizophrenia-1 (DISC1) – regulates glutamate release and neurotransmission across synapses. This discovery provides welcome progress to the development of targeted therapies for mental illness, a field facing decline as it has been plagued by detrimental side effects, high costs, and the inability to develop treatments to treat the disease rather than just the symptoms.

Glutamate is the main excitatory neurotransmitter in the brain. The release of glutamate from nerve terminals into the synaptic cleft underlies neuron-to-neuron communication in brain regions involved in higher cognitive functions, such as learning and memory, executive planning, and mental imagery. Not surprisingly, abnormal glutamate neurotransmission is linked to major psychiatric diseases, like schizophrenia, autism and bipolar disorder. However, pinpointing the cause of abnormal neurotransmitter release in these mental illnesses has been elusive.

Enjoying some time away from the bench. (L to R: Dr Farhan Mohammad, Asst Prof Adam Claridge-Chang, Dr Joses Lim)

Adam Claridge-Chang is Assistant Professor with the Neuroscience & Behavioural Disorders Programme at Duke-NUS Medical School. We talked to him about his most recent publication in Neuroscience & Biobehavioural Reviews: Concordance and incongruence in preclinical anxiety models: systematic review and meta-analyses.

Q: How did this paper come about?

Anxiety disorders are the most prevalent mental illnesses, but pharmaceutical companies have not been successful in finding effective treatments due to poor understanding of the underlying causes of mental illness. We were interested in finding new ways to understand anxiety by utilising the powerful genetic tools available in fruit fly (Drosophila melanogaster) research. Specifically,

Dr Farhan Mohammad, a talented postdoc in my lab, was working to set up a fruit fly model for anxiety. When he turned to the rodent anxiety literature to guide the development of the fly model, he was surprised to find a lack of consensus about which genes regulated anxiety. This posed an obstacle, since our strategy to validate the fly model relied on a direct comparison with preclinical data. At this point, conducting a meta-analysis seemed the best way to make sense of what the rodent data on anxiety was really telling us.



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