Allen laboratory: Central cardiovascular regulation
Andrew's research group has an overarching interest in how the central nervous system modulates cardiovascular function via the autonomic nervous system. This encompasses an interest in neuroscience, particularly how neural groups interact in vivo to generate specific motor patterns (in this case sympathetic activity to vascular smooth muscle), as well as the cardiovascular system. The following sections describe a few of our main areas of current interest.
Understanding the brain renin-angiotensin system.
Whilst its existence was suggested over 30 years ago, the brain renin-angiotensin system remains incompletely understood. Is angiotensin generated within the brain? If so, how does this happen when the constituents are present in different cell types (angiotensinogen in astrocytes; renin in very low concentration in some neurons)? Is angiotensin released from presynaptic terminals in response to depolarization- i.e. is it a neurotransmitter? These fundamental questions remain unanswered despite the fact that angiotensin is known to exert powerful actions in the brain on fluid and electrolyte homeostasis, autonomic activity, neuroendocrine function and neurodegenerative diseases.
Which neural pathways are involved in cardiovascular diseases?
Neural regulation of sympathetic and parasympathetic activity is clearly altered in cardiovascular diseases such as heart failure. In fact, alteration of this nervous activity is proposed to cause the hypertension that is a major risk factor for the development of these diseases. Yet, the neural circuits that regulate sympathetic and parasympathetic activity are incompletely understood. We are attempting to understand more about this circuitry in order to test fundamental questions such as:
- "Can a centrally-generated increase in sympathetic activity lead to sustained hypertension?"
- "Can we modify the progression of cardiovascular diseases by altering neural function?"
To answer these questions we are performing:
- viral transduction studies to alter gene expression in specific groups of neurons.
- specific drug administration to alter activity of certain neuron groups.
- opto- and pharmaco-genetic approaches to modulate the activity of neurons in vivo.
How do neurons interact?
With an estimated 1 billion neurons in the brain and each neuron potentially receiving information from hundreds of other neurons the potential interactions are mind-boggling. Reduced preparations are commonly used to try and bring the scale of these interactions to understandable proportions. We are trying to understand the mechanisms by which one of the simpler mammalian neural circuits works to generate activity. This is the circuitry responsible for the generation of sympathetic activity to blood vessels. We now know the constituent members of the circuit and their function on a broad level. This then brings us to an exciting point where we can look at:
- how individual neurons generate tonic activity
- how local synaptic interactions modify function
- how peptide neurotransmitters/neuromodulators change gain and might affect function in disease.
Dr Angelina Fong, Post-doctorate Fellow
Dr Clement Menuet, Post-doctorate Fellow
Angela Connelly, Research Assistant
Jaspreet Dosanjh, Research Assistant
Yan-Ting Choong, PhD Student
Nikola Jancovski, PhD Student
Nilanka Hettigoda, PhD Student
David Carter, PhD Student
Alya Dwiana, Masters Student
Damian Musci, Masters Student
2012-2014 Cell-selective deletion of brain AT1A receptors in hypertension: Effect on blood pressure, increased ROS production and inflammation. A.M. Allen. $558,675
2012-2014 Mapping the connectome that controls blood pressure. S. McMullan, A.K. Goodchild, A.M. Allen $320,000
- Hypothalamic modulation of basal sympathetic activity
- Angiotensin and chemoreceptor function
- Mapping the distribution of angiotensin receptors in the brain
- Understanding the role of angiotensin in the rostral ventrolateral medulla
- Understanding the aetiology of hypertension
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For further information about this research, please contact Professor Andrew Allen
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