Quick Project Snapshot
Neuroinflammatory mechanisms involved in hypertension and diabetes
Cardiovascular disease is a major cause of death in Australia, whereas diabetes is considered the fastest growing chronic condition worldwide having a devastating impact on quality of life. While current therapies target the symptoms of these diseases, the brain mechanisms that contribute to their underlying causes are unknown. A key common factor linking these diseases is diet-related brain inflammation that results in neurodegeneration. The pro-inflammatory molecule nuclear factor kB (NF-κB) seems to play an essential role in these mechanisms, by initiating the cytokine inflammatory cascade. Nevertheless, the changes in the autonomic nervous system that account for the development of hypertension and diabetes are still unknown.
This project will investigate the acute and chronic effects of NF-κB and its activator IkB kinase (IKKβ) in the area postrema. This area is essential for control of the sympathetic system, blood pressure, and blood glucose. We will use the following disease models: STZ-induced diabetic rats or 2 kidney 1 clip hypertensive rats. For instance, TNF-α pro-inflamatory cytokine related to NF-κB elicits increases in blood pressure (BP), and sympathetic nerve activity to the heart (CSNA) and kidney (RSNA).
The successful completion of the project will increase our understanding of whether NF-κB in the area postrema is a major contributor to the development of hypertension and diabetes. Additionally, it will determine if the blockade of the neuroinflamatory cascade ameliorates the symptoms of hypertension and diabetes.
The techniques to be used is this study are the following:
*small animal surgery (induction of diabetes or hypertension)
*electrophysiological preparation in anaesthetized rats
*microscopy (light, fluorescence)
Neurovascular Biology Laboratory
Our laboratory is focused on understanding how genetic, neurochemical and structural changes that occur in the brain following myocardial infarction contributes to an overactive sympathetic nervous system and consequently disease progression into heart failure. Current research projects include:
- Identifying and understanding the function of specific cytokines and their role in the brain in increasing sympathetic nerve activity to drive heart failure progression.
- Understanding blood-brain barrier function and how its integrity becomes compromised in cardiovascular diseases such as heart failure.
- Understanding the role of adult neurogenesis and how this might be important for regulating central cardiovascular control in health and disease.
We have recently shown that adult neurogenesis plays a critical role in the regulation of blood pressure. Using a synthetic analogue of the building blocks of DNA our group found that adult neurogenesis in the solitary tract is increased in both genetically and experimentally induced hypertensive models. The main challenge now is to understand how increased neurogenesis within the NTS contributes to hypertension. We believe this research will help us better understand the neurogenic origins of high blood pressure and reveal a new target for treating hypertensive patients.
All Projects by this LabCentral cardiovascular control: uncovering the role of inflammatory cytokines in the area postremaUnravelling the neural circuits that drive increases in sympathetic nerve activity in heart failureNeuroinflammatory mechanisms involved in hypertension and diabetes
In Systems Neurophysiology we seek to learn how the nervous system controls various bodily functions and how that control is altered in disease. Our disease focus includes not only neurological disorders such as epilepsy and multiple sclerosis, but also how the nervous system impacts on non-neurological diseases such as heart failure and inflammatory diseases. A clear understanding of basic mechanisms is crucial in developing better therapies and reducing the impacts of illness.