REACTIVE ASTROCYTES AND THEIR CONVERSION TO FUNCTIONAL NEURONS IN ISCHEMIC STROKE MOUSE MODEL

Open Access
Author:
Yellin, Emma V
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Tim Jegla, Honors Advisor
  • Gong Chen , Thesis Supervisor
Keywords:
  • in vivo reprogramming
  • stroke
  • NeuroD1
Abstract:
Previous research has shown that the expression of the transcriptional factor, NeuroD1, can efficiently reprogram reactive astrocytes into functional neurons in an Alzheimer’s disease mouse model (Guo et al., 2014). In this study, a stroke mouse model was used to investigate if NeuroD1 could convert reactive astrocytes of the glial scar into neurons. This investigation is important because it has the potential to produce an effective therapy for strokes, improving the lasting deficits caused by the injury. NeuroD1 was injected into the cortex of ischemic stroke mice, using an adeno-associated virus carrier. We then measured the expression levels of cellular markers such as NeuN, a neuronal marker, GFAP, an astrocyte marker, and C2PG and LCN2, which are reactive glial cell markers. We found that over time, the number of NeuN positive cells increases in mice that have had NeuroD1 injections, compared to the control group. We also found that GFAP, CSPG, and LCN2, which are generally upregulated in reactive cells, decrease in expression levels in NeuroD1 mice compared to the control. This suggests that NeuroD1 is able to create new neurons, while also decrease the signaling of reactive astrocytes in ischemic stroke mice.