Targeting Central Inflammation To Combat Obesity And Obesity-related Cognitive Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
The current obesity epidemic means many of us will suffer from overweight or obesity for at least some of our lives. My findings show obesity can cause inflammation throughout the brain including in regions related to learning and memory. Here I hypothesize that obesity induces long-term changes in the brain’s immune cells, that this can explain why we see susceptibility to cognitive decline in obese individuals, and that we can reverse these negative effects by targeting these immune cells.
Long-term Physical Exercise Improves Cognitive Performance Through Neuroimmune Modulation
Funder
National Health and Medical Research Council
Funding Amount
$493,586.00
Summary
This research investigates for how long exercise needs to carried out in order to be beneficial for cognitive function. We choose an animal model which simulates chronic brain inflammation as seen during aging processes of humans and during many inflammatory diseases affecting brain function. This research will unravel the long-term immunomodulatory and protective effects of exercise on brain function as well as the short-term anti-inflammatory effects on brain function.
Defining The Role Of Inflammation In Depression During Aging
Funder
National Health and Medical Research Council
Funding Amount
$736,820.00
Summary
This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depr ....This proposed research investigates the bidirectional relationship between inflammation in the central nervous system (CNS) and depression during normal aging processes. It is assumed that inflammatory processes in the CNS will induce the development of depression and vice versa, that depression will lead to increased inflammation in the body. In addition, the research will study the genetic background and gene expression of inflammation contributing to both aging processes and the onset of depression during aging.Read moreRead less
‘Chemobrain’: Neuroimmunological Consequences Of Chemotherapy-induced Mucositis And Opioid Palliation In Development Of The Condition
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Approximately 46% of cancer patients receiving chemotherapy will experience cognitive impairment. The development of this condition may be linked to another common gut side-effect of chemotherapy- mucositis. The treatment of mucositis pain by potent painkillers called opioids may also increase the risk of cognitive change. This project will determine the nervous system changes occurring in mucositis to identify targets for drug intervention to prevent development of cognitive decline.
Inflammation plays both protective and damaging roles in Alzheimer’s disease (AD), so to identify a long lasting and effective treatment, it is important that we better understand the underlying processes. Our studies implicate a cytokine called interleukin-18 (IL-18) as a factor that accelerates AD pathology. Here we propose to study the mechanisms by which this cytokine alters basic cell biological functions and how these changes affect AD pathogenesis.
Long-term Outcomes After Paediatric Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Traumatic brain injuries during early childhood often result in long-lasting issues including social behaviour problems and post-traumatic epilepsy. Using a unique model of brain injury in young mice, my research aims to identify the biology underlying the changes that cause these issues, and evaluate novel approaches to improve long-term outcomes after brain injury.
Functional Assessment Of CD40 In The Development Of Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$521,910.00
Summary
Many of the genes which affect susceptibility to Multiple Sclerosis (MS) have recently been identified. Two of these genes were first discovered in an Australian study published in Nature Genetics in 2009. One of these is CD40, which controls immune cell activation. In this project we aim to establish how the genetic variant identified affects the function of the CD40 gene in MS. CD40 may prove to be a good therapeutic target, with agents available to modulate CD40 available already.
Brain Pathways For Neurally-mediated Fever: From Vagal Afferent To Sympathetic Output To Brown Adipose Tissue Via Brain
Funder
National Health and Medical Research Council
Funding Amount
$405,223.00
Summary
Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins ....Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.Read moreRead less
REVERSIBLE AND IRREVERSIBLE TNF-MEDIATED COGNITIVE DECLINE
Funder
National Health and Medical Research Council
Funding Amount
$444,460.00
Summary
This proposal seeks to clarify the neuronal mechanisms underlying the inflammatory processing leading to cognitive decline. Furthermore, the research project identifies anti-inflammatory treatment options aiming at improved cognitive performance in people at risk for or suffering from cognitive impairment of neuropsychiatric disorders such as dementia and depression.