Beneficial Effects of NeuroD1-Mediated Direct Astrocyte-To-Neuron Conversion
Open Access
Author:
Mok, Yung Kin
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Dr. Gong Chen, Thesis Supervisor Richard W Ordway, Thesis Honors Advisor
Keywords:
glial scar NeuroD1 stab injury in vivo conversion glia to neuron ratio brain repair CNS injury astrocyte to neuron ratio direct reprogramming neuron regeneration
Abstract:
Central nervous system (CNS) injury often results in irreversible neuronal loss and consequent functional deficit. Limitation of adult neurogenesis and the neuroinhibitory role of reactive gliosis make neuron regeneration highly improbable. Previously, our lab developed a technology to convert glial cells to functional neurons in vivo via overexpression of a proneural transcription factor – NeuroD1. In this study, we employed a severe stab injury model in mouse cortex to demonstrate that NeuroD1 treatment can re-establish a healthy balance between neurons and astrocytes, thus reverting glial scar back into functional neural tissue. Furthermore, we reveal indirect beneficial effects associated with NeuroD1-mediated astrocyte-to-neuron conversion, such as reduced glial reactivity and their mediated neuroinflammation, restoration of the blood-brain barrier, and overall tissue regeneration. In summary, these results prove that NeuroD1-mediated astrocyte-to-neuron conversion aids CNS injury recovery both biochemically and physically.
