Thursday 21 September 2017 1:46pm
PhD student Hannah Best under the supervision of Dr Stephanie Hughes was awarded the Goddard Prize - the Best Student Oral Presentation at the 35th Australasian Winter Conference on Brain Research (AWCBR) held in Queenstown, 1-6 September 2017.
Take symptoms usually associated with Alzheimer’s, Parkinson’s and epilepsy. Combine this with motor dysfunction, blindness and a feeding tube in 4-9 year old children and you have Batten disease, a fatal genetic childhood neurodegenerative disease for which there are currently few treatments and no cure.
Hannah’s work focuses on two forms of the disease, aiming to understand the basic biology and develop rational therapies. Her studies showed reduced lysosomal and autophagic function, key components of the cellular recycling system in our cells and critical components for healthy neuronal function.
Using this information Hannah investigated current FDA approved drugs to mitigate these changes, first in neuronal cell cultures and then in a mouse model of Batten disease. These short term mouse studies showed a commonly used lipid lowering drug could reduce storage and neuroinflammation in the brain, howver also indicated differential drug effects between males and females. Longer term efficacy trials are currently underway.
PhD student Ashwini Hariharan under the supervision of Associate Professor Ping Liu was awarded the Best Student Poster Presentation at the 35th AWCBR held in Queenstown, 1-6 September 2017.
Alzheimer’s disease (AD) is the most common cause of dementia. Since the amyloid cascade hypothesishas been increasingly challenged due to clinical trial failure of amyloid-centred therapy, a critical question has been raised: Is amyloid beta the primary cause for the 95% of sporadic late-onset AD cases, or is it secondary to some other process? There is therefore an urgent need to explore other mechanisms.
Recent research has proposed that cerebrovascular endothelial dysfunction during advanced aging, together with other risk factors,triggers the neurodegenerative processes. Nitric oxide (NO) produced from L-arginine by endothelial NO synthase (eNOS) is a key regulator of cerebral blood flow dynamics. eNOS deficient (eNOS-/-) mice display age-related increases in amyloid beta in the brain and memory deficits, suggesting a critical role of eNOS dysfunction (hence cerebrovascular dysfunction) in the development of AD. Using a real-time microcirculation imager, Ashwini found that male and female eNOS-/- mice at 4 and 14 months of ages displayed abnormal increases in the blood perfusion in the Barrel cortex following the whisker stimulation relative to their age- and sex-matched wild-type controls. Moreover, the tissue concentrations of glutamine in the fontal cortex, hippocampus and parahippocampal region (the brain regions affected early and severely in AD) were dramatically reduced in eNOS-/- mice at both sexes and ages.
Ashwini’s work, for the first time, demonstrates early and long-lasting alterations in cerebrovascular coupling and glutamine metabolism in mice with eNOS deficiency. She is currently investigating the underlying mechanisms and functional significance of these changes.