Husna’s PhD Proposal

Asma Ulhusna Shaimi ( Husna ) joined BRAINetwork in September 2013. She has a Masters Degree in Chemistry from UKM and is currently a research assistant in BRAINetwork. She presented her PhD research proposal this morning in our meeting room. Her proposed study is related to the modulation of neurosteroidogenesis as a response to activation of neurocognitive pathways in the rat brain. Husna’s PhD research will be funded by a FRGS grant which was recently awarded to her two supervisors, Prof Dr Zalina Ismail (main supervisor) and Associate Prof Dr Tan Soo Choon (co-supervisor). Dr Hasmah Abdullah from the School of Health Sciences is aso a co-supervisor and Dr Wan Raihana Wan Asim from MTDC will be her field supervisor.

What is Husna’s project about? A brief summary is provided below:

Neurosteroids are endogenous steroids that are synthesised in the central nervous system. In the brain, neurosteroids modulate γ-aminobutyric acid A (GABAA), N-methyl-D-aspartate (NMDA) and sigma (σ) receptors. Additionally, neurosteroids act as neuroprotective and neurogenesis agents and regulators of memory and other neurocognitive functions. It has been demonstrated that neurosteroidogenesis is affected by external stimuli such as stress and exercise. However, it has yet to be established how neurosteroidogenesis is affected as a response to neurocognitive processes. There is a need for such information in order to form a firm basis for future research into the mechanisms of action for neurosteroids in relation to neurocognition. This is especially relevant as neurosteroids have been attracting interest as therapeutic agents for Alzheimer’s disease and other neurocognitive problems due to the promnesic properties of neurosteroids.

This study will attempt to explore the changes occurring in the levels of endogenous neurosteroids in specific areas of the brain in response to stimulation of spatial cognition, memory and executive function pathways of the rat brain. In order to achieve this, endogenous brain neurosteroids will be fluorescently labelled with monoclonal antibodies for the neurosteroids pregnenolone (PREG), PREG sulfate (PREGS), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS). Live, in-vivo visualisation and quantification of neurosteroids in the parietal, medial temporal and prefrontal regions of the brain will be performed in awake, freely-moving rats undergoing specific behavioural tests designed to stimulate specific neurocognitive pathways. Visualisation of the fluorescent neurosteroids will be performed with CellVizio® Lab (Mauna Kea Technologies, Paris, France), a probe-based, fibered fluorescence microscope that can be implanted into specific brain areas. Using this approach, it is hoped that this study will be able to provide new insights into the relationship between neurosteroidogenesis and neurocognition pathways.

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