Modeling The Two-hit Hypothesis Of Schizophrenia: Combined Neonatal Stress And Postnatal Corticosterone In Rats
Funder
National Health and Medical Research Council
Funding Amount
$318,500.00
Summary
Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions, social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this two-hit hypothesis in rats. We will compare the effect ....Schizophrenia is a severe mental illness defined by a number of symptoms including hallucinations, delusions, social withdrawal and cognitive impairment. Factors very early in development have been suggested to induce an increased vulnerability to this illness. Recently, it was suggested that another major event, later in life, would be needed before vulnerable individuals would develop schizophrenia. The aim of this project is to model this two-hit hypothesis in rats. We will compare the effect of various neonatal maternal separation protocols as an early stressful event, followed by chronic treatment with the stress hormone corticosterone at various stages later in life. We will also perform a detailed anatomical study of the hippocampus of these rats. This brain area has been implicated in the development of schizophrenia in humans. We will also investigate if treatment with antipsychotic drugs can prevent or reverse behavioural and neuroanatomical changes seen in the rats. This will be the first comprehensive study to model this two-hit neurodevelopment hypothesis of schizophrenia and will provide an experimental verification of a clinical concept which is very difficult to prove in patients.Read moreRead less
Interaction Of Oestrogen With The Serotonin-1A Receptor: Implications For Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$229,744.00
Summary
Gender differences have been observed in mental illnesses such as schizophrenia. It has been suggested that the female sex hormone, oestrogen, protects against schizophrenia, although how this occurs is unclear. This project aims to understand the mechanisms by which oestrogen interacts in the brain with major chemical systems (including serotonin and dopamine) that are implicated in the development and symptoms of schizophrenia.
Studying The Two Hit Hypothesis Of Psychiatric Illness: Role Of Brain-derived Neurotrophic Factor (BDNF)
Funder
National Health and Medical Research Council
Funding Amount
$469,553.00
Summary
Early environmental factors may play an important role in the development of psychiatric illnesses, such as schizophrenia and depression. We will study an animal model which combines early developmental stress followed by treatment with a stress hormone or chronic cannabis use in adolescence. We will assess behavioural changes and the role of a growth factor in the brain, BDNF. This wil lead to a better understanding of the role of neurodevelopmental stress in psychiatric disease.