Does Early Overnutrition Differentially Alter Hypothalamic Neuropeptides That Regulate Food Intake In The Rat
Funder
National Health and Medical Research Council
Funding Amount
$346,250.00
Summary
In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. I ....In Australia the incidence of obesity, in particular childhood obesity, is increasing dramatically, and the possible long term consequences of this are of great concern. The brain regulates appetite through a number of chemical transmitters such as neuropeptide Y (NPY) which is present in the brains of mammals and causes increased food intake. The effects of overeating from a young age on these brain transmitters has been largely ignored although this may impact on subsequent eating behaviour. In addition to NPY we will study other transmitters in the brain that have profound effects on appetite, some increasing, and others decreasing, food intake. These may form useful therapeutic targets for new drugs for obesity. Key targets we will study include melanocortins, glucagon-like peptide 1, urocortin, melanin concentrating hormone, agouti related peptide, and NPY. We will determine whether overnutrition from birth to weaning leads to changes in these appetite regulating neurotransmitters in the brain, and monitor the hormonal signals that impact on their activity. We will also determine whether early overnutrition exacerbates the subsequent responses to a high fat diet by comparison with rats made obese as adults. We will measure brain concentrations of the neurotransmitters, the amount released from the brain, and determine whether the feeding responses to injections of these agents is altered in obese animals. We have evidence that these transmitters interact in a co-ordinated fashion to affect feeding; this project will examine whether these interactions are maintained in the various types of obesity. Rats are commonly used for this type of study as the processes regulating feeding are very similar to those in humans and these agents cause similar effects in rats and humans. It is hoped that this information will provide new insight into the way brain adapts to overnutrition, and provide potential treatments for obesity and other feeding disorders.Read moreRead less
Changes In Motor Control And Kinaesthetic Sensations After Eccentric Exercise.
Funder
National Health and Medical Research Council
Funding Amount
$287,250.00
Summary
It is a well-known observation that after a period of intense exercise we are unsteady on our feet and are clumsy when attempting to make precision movements. Such impressions are particularly marked after eccentric exercise, during which the contracting muscles are forcibly lengthened. Activities such as walking downhill, skiing and horse riding involve eccentric exercise. The debilitating consequences of this kind of exercise are attributed, not just to the post-exercise effects of fatigue, bu ....It is a well-known observation that after a period of intense exercise we are unsteady on our feet and are clumsy when attempting to make precision movements. Such impressions are particularly marked after eccentric exercise, during which the contracting muscles are forcibly lengthened. Activities such as walking downhill, skiing and horse riding involve eccentric exercise. The debilitating consequences of this kind of exercise are attributed, not just to the post-exercise effects of fatigue, but to loss of muscle force from damage to fibres. Eccentric exercise also leads to longer term effects. The breakdown of the damaged tissue leads to sensations of stiffness and soreness the next day. This application proposes experiments aimed at studying a number of effects of eccentric exercise on motor control, and establishing the muscle, spinal and brain levels at which they occur. Three studies are planned. In the first, the question will be explored whether we are less able to use the motor areas of our brains to execute voluntary contractions after exercise. So fatigue is not just a matter of exhausted muscles but perhaps also exhausted brains. We will use brain and spinal cord stimulation to explore this point. Then we plan to listen to single motor units, the basic elements of muscle control, to try to understand the mechanism by which the brain minimises the debilitating effects of fatigue. Finally we want to examine subjects' ability to locate their limbs in space as a means of providing a basis for the clumsiness we experience after intense exercise. These are all important issues relevant to clinical medicine and rehabilitation as well as sports science and exercise.Read moreRead less
Ghrelins Novel Neuroprotective Effects In Parkinsons Disease Are Mediated By AMP-activated Protein Kinase (AMPK).
Funder
National Health and Medical Research Council
Funding Amount
$400,885.00
Summary
Studies show that body mass index, midlife adiposity and diabetes are associated with Parkinson's disease (PD). During obesity there is a dramatic change in nutritional information, such as hormones, sugars and fats, carried in the blood. This proposal explores how this altered nutritional information in obesity kills the brain cells associated with PD. It will examine how ghrelin, a metabolic hormone inversely related to obesity, influences and protects brain cell activity in models of PD.
Intraocular Transplantation And Regeneration Of Retinofugal Pathways In Rodents
Funder
National Health and Medical Research Council
Funding Amount
$370,937.00
Summary
In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replen ....In the adult human brain and spinal cord there is little or no intrinsic capacity for replacement of lost or dying neurons, and there is minimal spontaneous repair of nerve fibre pathways. Thus traumatic injuries, stroke, or loss of neurons due to chronic degenerative disease result in functional impairments that are usually severe and long-lasting. The personal, social and economic costs associated with these neurological problems are enormous. New ways must be found of protecting and-or replenishing nerve cells in damaged CNS gray matter, and new methods are also required to help reconstruct fibre tracts after injury. Using the visual system as an experimental model, the aims of the proposed work are to develop novel transplantation and surgical strategies to: (i) Incorporate new cells into retinae that have been selectively depleted of endogenous neurons (ii) Promote the effective regeneration of large numbers of adult retinal axons through prosthetic peripheral nerve bridging grafts and into host CNS distal to the injury. The results obtained from the first series of studies will not only be of direct relevance to the future treatment of human retinal degenerative disorders, but will also increase our overall understanding of how best to ensure the differentiation and stable integration of different types of transplanted cells within the compromised host CNS. The second series of experiments should lead to an entirely new approach to nerve pathway reconstruction, relevant to both brain and spinal cord injuries. The ultimate aim of this experimental work is to improve the management and treatment of human CNS injury and disease, leading to better functional recovery and rehabilitation.Read moreRead less