Disturbed Calcium Dynamics in the Brain: A Precursor to Alzheimer's
The figure shows a sketch of the neurovascular unit, NVU (left), a tissue block with embedded vascular tree (centre) and a sketch of the tissue slice placed into the cerebral cortex (right)
The BRATS research group is looking to investigate the calcium dynamics in the brain to understand if failing of local bloodflow regulation is a precursor to Alzheimer’s Disease.
The brain has a specific mechanism that ensures a sufficient and continuous supply of nutrients in the face of changing local demand and physiological conditions. “Neurovascular coupling" is the ability to increase blood flow and hence oxygen and glucose supply to neurons when they become more active. It occurs predominantly by linking neurons to the smooth muscle cells surrounding blood vessels via the astrocytes (star-shaped cells that connect neurons and vasculature).
The prevalence of Alzheimer’s Disease increases exponentially as the global population ages, more than 15% of people aged 65 years and older experience cognitive impairment, and almost half at the age of 85 have dementia. Neuronal survival critically depends on neurovascular coupling and vascular dysfunction is a critical factor in Alzheimer’s Disease pathophysiology.
Our aim is to provide a numerical model of the regulated blood supply with connected cells for the whole brain, which includes the complex calcium dynamics in neurons and astrocytes. We want to investigate the effect calcium has on the neuronal function and how it is disturbed from its non-pathological equilibrium. In particular we will concentrate on simulating the role of the calcium-mediated TRPV4 ion channel which has been shown to be enhanced under amyloid beta concentration and to contribute to hippocampal damage.
The project is being supervised by professor Tim David (UC HPC) and includes UC PhD student Katharina Dormanns. It is funded by a Canterbury Medical Research Foundation project grant and includes high-performance computing using the UC HPC power7.
The outcome of this research will allow new insights into the pathophysiological abnormalities that significantly precede overt clinical symptoms. This may open up new therapeutic targets associated with the vascular system, whilst providing a non-invasive physiological biomarker that can be tracked and allow for pre-clinical therapeutic intervention.
by Katharina Dormanns