Microglia, the guardians of the CNS, are the resident tissue macrophages and constitute –10% of the total cells in the adult brain. They perform homeostatic activity in the healthy brain, a function associated with the high mobility of their processes that scan surrounding area constantly and phagocytic clearance of extracellular debris. During brain injury and disease they are capable of responding quickly to disturbances in tissue homeostasis by altering their morphology and acquiring the so called “activated state”. Morphologically activated microglia exists as many different phenotypes depending on the insult corresponding to a vast array of specific responses.
Whether microglia play a harmful or a beneficial role during neurodegenerative disorders such as Alzheimer disease(AD) has been a matter of discussion in the last few decades. Recent advances in understanding the pathogenesis of AD characterized by accumulation of fibrillar β-amyloid, highlight the importance of these professional phagocytes as key players in the genesis and modulation of the disease.
Efficient clearance of Aβ is essential in maintaining an healthy brain and in the light of this notion, enhancing microglia phagocytic activity might constitute a possible therapeutic target.
The road of harnessing the immune system as a way of lowering Aβ burden in diseased brain has already been taken in the past through Aβ immunization, both in mouse models and in humans, though results have been widely inconclusive. Further investigation is needed to fully comprehend the role of microglia and neuroinflammation in disease pathogenesis and thus applying the right course of action in developing a treatment.
My thesis research in the lab of the Scuola Normale Superiore focuses on the relationship between microglia, NGF and Alzheimer’s Disease. Our lab uses a particular AD mouse model, AD11, which expresses an antibody against NGF(αD11). This model presents Aβ plaques and cognitive impairment at an early age and thus constitutes a good model for AD. In previous studies on this model, various changes in the inflammatory landscape have been identified, suggesting the possible role of microglia as the primary effector of NGF deprivation. My work consists primarily in identifying specific changes in this cell type under the action of αD11 to assess whether microglial activation might be responsible for AD11 phenotype.
The main points of my research involve:
• Characterization morphology and activation of microglia in the AD11 brains;
• In vitro studies: treatment with αD11 on primary microglia to investigate the inflammatory state induced by NGF deprivation.
This project entails the use of IHC, ICC, confocal imaging, RT PCR, WB
