Early Stage Researcher 11/12 – Rita Silva

Individual Research Project 11/12
Project Title: Neuroinflammation and CNS hyper-excitability in chronic pain and neurodegeneration mice models
Supervisor: Dr. Emanuele Sher (Eli Lilly)
Co-supervisor(s): Prof. M. Malcangio (KCL)

The co-morbidity of AD and chronic pain in the growing ageing population needs to be addressed if proper pain control in AD patients is to be achieved. The beneficial versus detrimental role of neuroinflammation, and the time-dependency of neuroinflammation-mediated mechanisms, are still heavily debated. This project proposes that neuro-inflammation plays a significant, and possibly differential, role in the sensory versus cognitive/affective components of chronic pain under neurodegenerative conditions.

ESR 11/12 will:

1. Examine spinal cord and brain neuroinflammation at biochemical, morphological and electrophysiological levels in 1) models of chronic pain (inflammatory, CFA model);
2. Models of spinal and brain neurodegeneration (tau overexpressing P301S and tg4510 mice);
3. Models of combined pain and neurodegeneration. The focus will be on microglia/astrocytic mechanisms, including the mechanisms controlling the production and release of pro-inflammatory cytokines and neurotrophic factors (ELISA). Synaptic transmission, excitability and plasticity properties as well as changes in these parameters after in vitro or in vivo administration of drugs affecting glial mechanisms (e.g. P2X7 receptor antagonists) will be studied in acute spinal cord and brain slices from the models above.

Definition of the impact of inflammation, cytokines, and neurotrophins on spinal cord and brain synaptic transmission and excitability. 2) Develop a translational mouse model for the study of neuroinflammation and pain/cognition/affective comorbidities in AD.

Secondment(s): KCL (4 months). Cytokines and neurotrophins ELISA measurements in spinal cord, brain and CSF. Cytokines and neurotrophins evaluation at the immunohistochemical level in spinal cord and brain.