Grant: Operating Grant

Schizophrenia is a debilitating human mental disorder affecting about 1% of the population (approximately 400,000 people in Canada). This disease can manifest in various ways, and is characterized by positive symptoms (hallucinations,delusions, disorganized behaviour), negative symptoms (poverty of speech, lack of emotional experience, inability to experience pleasure, lack of social interaction, attention impairment), and cognitive dysfunction. While symptom types are independent from each other, they can co-exist in the same patient. Unfortunately, the cause of schizophrenia is unclear and currently available drug treatments for this illness are not without severe side effects. This project deals with a protein called synapsin II found in the presynaptic site, the site from which chemicals called neurotransmitters are released. Recent works from various laboratories, including our own, have demonstrated the role of synapsin II in the neurobiological mechanisms involved in schizophrenia. The preclinical animal model developed in our laboratory mirrors the behavioural abnormalities displayed by subjects with schizophrenia. Further studies proposed in this application will greatly advance our understanding of this mental illness. This project will investigate the role of synapsin II at pre-pubertal and post-pubertal stages (adulthood), and its effect on the development and progression of schizophrenia. A combination of several technologies (brain imaging, gene expression, estimation of behavioural abnormalities by computerized systems, immunohistological techniques) will be used to answer fundamental questions. By understanding the potential mechanistic role of decreased synapsin II in the brain region called the medial prefrontal cortex in the pathophysiology of schizophrenia, progress can be made towards a better understanding of this devastating mental illness and the development of novel therapeutic approaches with higher specificity and fewer adverse effects.