Relationship Between Anterior Cingulate Morphology, Neuronal Integrity And Function In Schizophrenia And OCD
Funder
National Health and Medical Research Council
Funding Amount
$312,813.00
Summary
Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface betw ....Schizophrenia and obsessive-compulsive disorder (OCD) are extremely disabling psychiatric disorders. Both tend to appear in early adulthood and have a number of important similarities. These include problems with planning and organising thoughts, abnormal brain chemistry, and changed function in the same brain region, the anterior cingulate. The anterior cingulate has been known for some time to be involved in emotion, motivation and attention. However, it is now recognised as the interface between the emotional, feeling part of the brain and the controlling, thinking part. Many, if not all, of the functions performed by the anterior cingulate are disturbed in both schizophrenia and OCD, meaning that studying this region may provide important clues to the nature of the two illnesses. One important characteristic of the anterior cingulate which has not been considered in previous research is its division into three distinct subregions, each with their own specific function. In particular, there is a cognitive region, which deals with response selection and information processing, and an emotional region, which assesses motivational content and controls emotional learning. Because of the nature of the two disorders we intend to study, we believe that schizophrenia will be associated with more abnormalities of the cognitive region, while OCD will be associated with changes in the emotional region. Another important feature of our research design is that we intend to collect data from the same subjects using four separate brain imaging techniques, which provide information about different levels of brain structure and function. This will allow us to interpret our findings from measures of brain chemistry in the context of our findings of brain function. Hopefully this will help us to clarify the pathophysiology of schizophrenia and OCD, and provide potential ways to assess the effect of different treatment strategies in these illnesses.Read moreRead less
THE ROLE OF RESIDENT MAST CELLS IN ISCHAEMIA-REPERFUSION INJURY OF SKELETAL MUSCLE.
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the blood-oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected to more injury, which is thought to be caused by oxygen and-or white blood cells. This type of injury occurs in muscle which has been crushed, limbs that have been broken or traumatized, in ....NHMRC 209113 LAY DESCRIPTION Ischaemia reperfusion injury occurs in skeletal muscle when the blood-oxygen supply is cut off (ischaemia) and later restored (reperfusion). If the duration of ischaemia is short some of the muscle survives. However, when blood flow and oxygen are restored the muscle is subjected to more injury, which is thought to be caused by oxygen and-or white blood cells. This type of injury occurs in muscle which has been crushed, limbs that have been broken or traumatized, in replantation of amputated parts, in transplantation, after some surgical procedures and after microsurgical transfer of muscle. Once established there is no effective treatment. Our experiments show that a particular cell, the mast cell, and a particular molecule, nitric oxide, are involved in causing ischaemia reperfusion injury. However, the extent of their involvement is unknown. In this proposal we will investigate the effect of replacing mast cells into muscles, in a unique variety of mice which normally don t contain mast cells and are resistant to ischaemia reperfusion injury. In one group of mice we will put back normal mast cells and in a second group of mice we will put back mast cells that cannot produce the nitric oxide molecule. These experiments will determine, unambiguously, the extent of involvement of mast cells and mast cell-derived nitric oxide. In the second part of this proposal will carry out a time course study, using pharmacologically induced mast cell degranulation, to determine when the mast cells become injurious to skeletal muscle. These experiments will identify the period during which mast cell behaviour can be modulated in order to protect the muscle from ischaemia reperfusion injury. Determination of the role of mast cells, and an understanding of the timing during which they become injurious would provide a logical basis for optimizing drug therapy in clinical applications of these findings.Read moreRead less
In the areas of the brain where visual information is processed, cells respond to the presentation of visual stimuli by changing their pattern of electrical activity. At the first level of analysis, the primary visual cortex (V1), individual cells become active only if line segments or borders of a particular orientation are present in their field of detection, which encompasses a small part of the visual scene. Cells in other visual cortical areas (the extrastriate cortex) perform more complex ....In the areas of the brain where visual information is processed, cells respond to the presentation of visual stimuli by changing their pattern of electrical activity. At the first level of analysis, the primary visual cortex (V1), individual cells become active only if line segments or borders of a particular orientation are present in their field of detection, which encompasses a small part of the visual scene. Cells in other visual cortical areas (the extrastriate cortex) perform more complex detection tasks in comparison with those in V1, which demand integration of information coming from much larger portions of the visual scene. One example of these more complex properties is the phenomenon of long-range contour integration, where our visual system groups individual line segments having similar orientations, so that they are perceived as part of the same contour. This property is reflected in the electrical responses of cells in the dorsomedial visual area (DM). How are properties such as orientation specificity and long-range contour integration created? To begin addressing this question, we will investigate correlations between the physiological properties of identified cells, the spatial distribution of their information collecting regions (dendrites), and the anatomical pathways by which they receive information from other parts of the brain. This is a basic science study aimed at determining the extent to which the anatomical structure of the brain helps define the function of individual cells and brain areas. Its primary benefit will be to increase our understanding of the mechanisms underlying all sensory processing in the brain. The knowledge obtained may also lead to developments in areas of applied research including medicine and cognitive science (for example, understanding how the brain learns to interpret visual information in early life, and how visual processing degrades with ageing).Read moreRead less
The Role Of Renin-angiotensin And Growth Factors In Developmental And Pathological Neovascularization In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$342,562.00
Summary
In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some ....In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some eye diseases new blood vessel growth is excessive and the vessels are not properly formed, which leads to hemorrhage and ultimately blindness. Such events occur when the oxygen environment of premature babies is reduced after placement in high oxygen incubators. Also, in long-term diabetes, the oxygen levels of the retina falls as the retinal vessels become damaged. To understand the events that cause new vessel growth in retinal development and disease requires identification of the growth agents and their location in the retina. Very recently it has been found that the growth agent renin-angiotensin is made in the retina, and that its blockade in diabetic patients slows the progression of new retinal vessel growth. Renin-angiotensin is likely to cause its growth effects by increasing the production of other retinal growth agents. This proposal will study the role of renin-angiotensin and other growth agents in the developing newborn rat retina and in eye diseases. This information may lead to a further understanding of how blood vessels form in the retinas of newborn babies, and the production of new treatments for eye diseases characterized by blood vessel growth in the retina.Read moreRead less