Imaging Genetics In Schizophrenia And Bipolar Disorder: Adjudicating Neurocognitive Endophenotypes
Funder
National Health and Medical Research Council
Funding Amount
$569,873.00
Summary
Schizophrenia and bipolar disorder share some common genes and cognitive deficits, yet manifest differently in terms of symptom expression, illness course, and functional impact. This research tests the assertion that genes implicated as common to these conditions may code for impairments in prefrontal cognitive and sub-cortical emotion processing. We also examine whether between-diagnosis distinctions in these brain responses may be mediated by hypothalamic-pituitary-adrenal axis functioning.
Neurons in the two hemispheres of the brain make connections with each other via a large fibre tract called the corpus callosum. In over fifty different human congenital syndromes the corpus callosum fails to form properly. Such syndromes, which include Aicardi syndrome, Andermann syndrome, Shapiro syndrome and Acrocallosal syndrome, can result in mental retardation, seizures, lack of motor coordination and ocular abnormalities in children. Our data on both mouse and human brain development show ....Neurons in the two hemispheres of the brain make connections with each other via a large fibre tract called the corpus callosum. In over fifty different human congenital syndromes the corpus callosum fails to form properly. Such syndromes, which include Aicardi syndrome, Andermann syndrome, Shapiro syndrome and Acrocallosal syndrome, can result in mental retardation, seizures, lack of motor coordination and ocular abnormalities in children. Our data on both mouse and human brain development show that the mouse is an excellent model system for understanding how the brain becomes wired up during development and what may go wrong in these disorders. Here we investigate the role of a family of genes called nuclear factor one (Nfi) genes in brain development. When mutated in mice, members of this gene family, principally Nfia and Nfib, cause severe malformations of the brain. The phenotype inlcudes a failure to form some midline glial populations, the expansion of the cingulate cortex and loss of the corpus callosum. The propoer formation of midline glial populations and the cingulate cortex are essential to callosal fomration and correct brain wiring. Defects in brain wiring in the cingulate cortex during development may underlie disorders such as schizophrenia, bipolar disorder and depression. In this project we will address the mechanism of function underlying the control of brain development by the Nfi genes. The expected outcomes of this research are to identify new mechanisms and genetic pathways critical to the formation of connections between the two sides of the brain and proper formation of the cingulate cortex. These results will improve our understanding of how the brain forms and what mechanisms may be disrupted during development that result in neurological and cognitive deficits in children and adults.Read moreRead less
Role Of Chromatin Structure In The Regulation Of Stem Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$272,036.00
Summary
The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can b ....The aim of this project is to understand more about the nature of stem cells. Stem cells are cells which have the capacity to proliferate indefinitely but, at the same time, retain the capacity to differentiate into one or more cell types. Lower animals, such as amphibians, have a much greater capacity than humans to regenerate body parts. For example, axolotls can regenerate an entire limb if one limb is injured. This is because they retain undifferentiated stem cells in their limbs which can be reactivated in the event of injury. Interestingly the adult human brain contains a small population of stem cells. The aim of this project is to find out more about how these cells remain undifferentiated and what is it about them which allows them to form different cell types. If more is known about these cells maybe in the future it will be possible to stimulate them to repair damaged parts of the nervous system. It may also be possible to treat people suffering from diseases like Alzheimer's disease, Parkinson's disease or spinal injuries.Read moreRead less