NeuRA Magazine #20

NOVEL INSIGHTS INTO DOPAMINE DYSFUNCTION

Understanding how more precisely dopamine is changed in the brains of people with schizophrenia will help us to better understand the main path that leads to developing the disorder.

Dr Tertia Purves Tyson

While there are many roads leading to the development of schizophrenia, one often considered a final common pathway is the dysregulation of dopamine. Too much dopamine in particular region of the brain – the subcortex – contributes to the psychotic symptoms seen in schizophrenia.

Dopamine is a neurotransmitter that helps to control the brain’s reward and pleasure centre, and regulates our emotions. Antipsychotics are designed to block dopamine receptors, and reduce the amount of dopamine action in the brain. Unfortunately, antipsychotics do not work for everyone and have serious side effects.

A better understanding of how and where dopamine is changed in the brains of people with schizophrenia will help us to understand how to more accurately correct or prevent this disruption and thus help to design more targeted approaches to treatment.

A new study from the Schizophrenia Research Lab has identified molecular changes in the brains of people with schizophrenia, which offers support for and extends the dopamine hypothesis.

The new study from Dr Tertia Purves-Tyson compared tissue from deep in the brain (midbrain) of people with and without schizophrenia. This brain region has not previously been given the attention it deserves in schizophrenia research on human brains donated after death. The study found that the genes of molecules that are responsible for regulating the amount of dopamine and for regulating the reaction to dopamine (receptors) are altered in people with schizophrenia.

These alterations in gene expression implicate a new suspect as a major contributor to dopamine dysregulation, namely a massive decrease in dopamine transporter. This 66% reduction in this important molecule would mean that dopamine may be allowed to stay in the synapse longer than it should and suggests that novel treatments aimed at ramping up the synthesis and function of this in schizophrenia could be of benefit. To our knowledge, dopamine transporter has not been used as a treatment target ever before.

This study begins to address a vital knowledge gap in schizophrenia research with regards to how dopamine in the midbrain contributes to dopamine dysfunction. This will help us to better understand the dopamine dysregulation that is found in schizophrenia and, potentially, how we can better treat it.

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FEEL THE BUZZ IN THE AIR? US TOO.

During three decades on Australian television, two simple words brought us to attention.

‘Hello daaaahling’. Outrageous, flamboyant, iconic – Jeanne Little captivated Australians everywhere with her unique style, cockatoo shrill voice and fashion sense. "Mum wasn't just the life of the party, she was the party.” Katie Little, Jeanne’s daughter remembers. This icon of Australian television brought a smile into Australian homes. Tragically, today Jeanne can't walk, talk or feed herself. She doesn't recognise anyone, with a random sound or laugh the only glimpse of who she truly is. Jeanne Little has Alzheimer's disease. The 1,000 Brains Study NeuRA is very excited to announce the 1,000 Brains Study, a ground-breaking research project to identify the elements in our brains that cause life-changing neurodegenerative diseases like Alzheimer’s, Parkinson’s and other dementias. This study will focus on the key unresolved question: why do some of us develop devastating neurodegenerative diseases, while others retain good brain health? The study will compare the genomes of people who have reached old age with healthy brains against the genomes of those who have died from neurodegenerative diseases, with post mortem examination of brain tissue taking place at NeuRA’s Sydney Brain Bank. More information on the study can be found here. Will you please support dementia research and the 1,000 Brains Study and help drive the future of genetics research in Australia? https://youtu.be/q7fTZIisgAY
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