Source Paper
Regulation of Microglial Proliferation during Chronic Neurodegeneration
Diego Gómez-Nicola, Nina L. Fransen, Stefano Suzzi, V. Hugh Perry
Journal of Neuroscience • 2013
Mouse Prion Disease Model
Objective: Study the time course and regulation of microglial proliferation using a mouse model of prion disease to understand microglial expansion and identify molecular regulators of the proliferative response during chronic neurodegeneration
Protocol Steps
Establish mouse model of prion disease
Use a mouse model of prion disease to study the time course and regulation of microglial proliferation and the expansion of the microglial population during disease development
Note: The model is used to examine microglial and astroglial cell proliferation and activation as components of chronic neurodegenerative disease
View evidence from paper
“We studied the time course and regulation of microglial proliferation, using a mouse model of prion disease.”
Analyze microglial proliferation and population expansion
Examine the proliferation of resident microglial cells and their contribution to population expansion during disease development
Note: Results show that proliferation of resident microglial cells accounts for the expansion of the population during disease development
View evidence from paper
“Our results show that the proliferation of resident microglial cells accounts for the expansion of the population during the development of the disease.”
Identify molecular regulatory pathways
Identify the pathway regulated by activation of CSF1R and the transcription factors PU.1 and C/EBPα as molecular regulators of the microglial proliferative response
Note: These pathways correlate with chronic human neurodegenerative conditions including variant Creutzfeldt-Jakob disease and Alzheimer's disease
View evidence from paper
“We identify the pathway regulated by the activation of CSF1R and the transcription factors PU.1 and C/EBPα as the molecular regulators of the proliferative response”
Test CSF1R inhibition effects
Target the activity of CSF1R to determine effects on microglial proliferation, neuronal damage, and disease progression
Note: CSF1R inhibition was shown to inhibit microglial proliferation and slow neuronal damage and disease progression
View evidence from paper
“We show that targeting the activity of CSF1R inhibits microglial proliferation and slows neuronal damage and disease progression.”