Department Neuroscience Research
Age-related neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease and stroke are increasingly consuming larger amounts of Singapore’s healthcare budget, and the social burden weighs on the community. The Anatomy Department has therefore made age-related neurodegenerative diseases, a major research area. Work is carried out by a broad-based group of investigators who conduct inter-disciplinary research in: (1) chemical neuroanatomy of the brain (2) gliobiology, and (3) translational neuroscience for repair of the damaged nervous system.
Research on chemical neuroanatomy is focused on translational aspects of phospholipid, sphingolipid and cholesterol biology in the CNS, with the view of elucidating the localization and function of lipid mediators and their biosynthetic enzymes or receptors in normal and pathological conditions. Gliobiology research is focused on the role of microglia in health and disease - in the brain and eye (retina). Highlights include elucidating the role of transcription factors such as Runx1t1, histone modifiers such as sirtuin 3, miRNA and other non-coding RNAs, and natural compounds such as scutellarin in regulating the signaling pathways for microglial activation, that can result in neuroinflammation and neuronal death after brain injury. Attention is also given to interactions between microglia and astrocytes and neurons; as well as the blood-brain barrier, the blood-retinal barrier and the choroid plexus, which may be damaged and sites of lymphocyte and macromolecule entry into the brain during disease states, including neonatal hypoxia. Research on oligodendrocytes has identified juxtanodin which plays an important role at the node of Ranvier, a novel ligand of the Notch receptor which plays a prominent role in differentiation and maturation of oligodendrocytes, and a new population of small non-coding RNAs essential for maintaining stem cell pluoripotency. Research on astrocytes has revealed defects in mir-31a affect glial homeostasis in the adult drosophila brain.
All the above research is conducted with the view of translating the findings to the clinics. In this regard, special advance has been made, using miRNA mimics or knockdown to attempt to reverse free radical damage and symptoms of Parkinsonism in vitro and in a monkey model; and tissue engineering approaches in collaboration with bioengineers, to repair the damaged spinal cord e.g. using neurotrophin releasing or stem/Schwann cell-engrafted scaffolds.