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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Brain and Knee Muscle Weakness Study

Why Does Quadriceps Weakness Persist after Total Knee Replacement? An Exploration of Neurophysiological Mechanisms Total knee replacement is a commonly performed surgery for treating end-staged knee osteoarthritis. Although most people recover well after surgery, weakness of the quadriceps muscles (the front thigh muscles) persists long after the surgery (at least for 12 months), despite intensive physiotherapy and exercise. Quadriceps muscle weakness is known to be associated with more severe pain and greatly affect daily activities. This study aims to investigate the mechanisms underlying weakness of the quadriceps muscles in people with knee osteoarthritis and total knee replacement. We hope to better understand the relationship between the changes of the brain and a loss of quadriceps muscle strength after total knee replacement. The study might be a good fit for you if you: Scheduled to undergo a total knee replacement; The surgery is scheduled within the next 4 weeks; Do not have a previous knee joint replacement in the same knee; Do not have high tibial osteotomy; Do not have neurological disorders, epilepsy, psychiatric conditions, other chronic pain conditions; Do not have metal implants in the skull; Do not have a loss of sensation in the limbs. If you decide to take part you would: Be contacted by the researcher to determine your eligibility for the study Be scheduled for testing if you are eligible and willing to take part in the study Sign the Consent Form when you attend the first testing session Attend 3 testing sessions (approximately 2 hours per session): 1) before total knee replacement, 2) 3 months and 3) 6 months after total knee replacement. The testing will include several non-invasive measures of brain representations of the quadriceps muscles, central pain mechanisms, and motor function and questionnaires. Will I be paid to take part in the research study? You will be reimbursed ($50.00 per session) for travel and parking expenses associated with the research study visits. If you would like more information or are interested in being part of the study, please contact: Name: Dr Wei-Ju Chang Email: w.chang@neura.edu.au Phone: 02 9399 1260 This research is being funded by the Physiotherapy Research Foundation.  
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