Early Activation of Microglia Triggers Long-Lasting Impairment of Adult Neurogenesis in the Olfactory Bulb

• DOI: 10.1523/jneurosci.6394-11.2012
• Publication Date: 2012-03-14T18:09:12Z
• Authors: Françoise Lazarini; Marie-Madeleine G...; Nicolas Torquet; Pierre-Marie Lledo
• Keywords: MESH: Olfactory Bulb; Male; Time Factors; Cell Survival; Neurogenesis; microglia; MESH: Mice, Knockout; Mice; 03 medical and health sciences; MESH: Mice, Inbred C57BL; MESH: Smell; Animals; MESH: Animals; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; MESH: Mice; MESH: Age Factors; Mice, Knockout; 0303 health sciences; MESH: Time Factors; Age Factors; Olfactory Bulb; MESH: Male; MESH: Neurogenesis; MESH: Microglia; adult neurogenesis; Mice, Inbred C57BL; Smell; MESH: Cell Survival; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Microglia

Microglia, the innate immune cells of the brain, engulf and eliminate cellular debris during brain injury and disease. Recent observations have extended their roles to the healthy brain, but the functional impact of activated microglia on neural plasticity has so far been elusive. To explore this issue, we investigated the role of microglia in the function of the adult olfactory bulb network in which both sensory afferents and local microcircuits are continuously molded by the arrival of adult-born neurons. We show here that the adult olfactory bulb hosts a large population of resident microglial cells. Deafferentation of the olfactory bulb resulted in a transient activation of microglia and a concomitant reduction of adult olfactory bulb neurogenesis. One day after sensory deafferentation, microglial cells proliferate in the olfactory bulb, and their numbers peaked at day 3, and reversed at day 7 after lesion. Similar lesions performed on immunodeficient mice demonstrate that the both innate and adaptive lymphocyte responses are dispensable for the lesion-induced microglial proliferation and activation. In contrast, when mice were treated with an antiinflammatory drug to prevent microglial activation, olfactory deafferentation did not reduce adult neurogenesis, showing that activated microglial cells per se, and not the lack of sensory experience, relates to the survival of adult-born neurons. We conclude that the status of the resident microglia in the olfactory bulb is an important factor directly regulating the survival of immature adult-born neurons.