2008 Brain Star Award Recipient - Bahareh Ajami
Recipient
Bahareh Ajami - Biosketch
PhD (Experimental Medicine)
University of British Columbia
Article
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM. Nat Neurosci. 2007 Dec; 10(12):1538-43
Significance of the paper
Microgliosis is a common response to multiple types of damage within the Central Nervous System (CNS). Yet, the origin of the cells involved in this process and the mechanisms regulating microglia homeostasis is the subject of controversy. The majority of literature based on chimeric mice generated by bone marrow transplantation in irradiated recipients suggest that microgliosis involves resident microglial cells as well as the recruitment of bone marrow-derived cells, which migrate through the circulation, enter the brain parenchyma through the blood brain barrier and differentiate into microglia.
However, our data obtained from parabiosis model in which peripheral blood chimerism was obtained in absent of irradiation and transplant , suggest that in adult animals microglia maintenance and function are independent of bone marrow-derived progenitors throughout the adult life, and that microglia within the CNS is capable of self-renewal.
Our paper adds a major contribution to the current dispute on the mechanism underlying microglial cells maintenance and expansion. More importantly, this work could also lead to a more careful interpretation of a vast body of literature on the role of blood-derived myelomonocytic cells in two neurological disorders: facial nerve axotomy and Amyotrophic Lateral Sclerosis, which are mostly based on irradiation chimeras.
Furthermore, our findings lay the basis for the future identification and purification of bone marrow progenitors retaining microglial potential. Such progenitors may allow the specific repopulation of the CNS microglial compartment without concurrent repopulation of the bone marrow; thus, it allows gene delivery to the CNS while avoiding the problems associated with the use of engineered hematopoietic stem cells (e.g. vastly increased risk of leukemia) by expanding in situ independently of the contribution of bone marrow-derived circulating progenitors.