027 – Smoking mice: analysis of the effect of cigarette smoke on hippocampal microglia

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027 – Smoking mice: analysis of the effect of cigarette smoke on hippocampal microglia

Fernando Gonzalez Ibanez (1) – Julien Blouin (1) – Amin Benadjal (2) – Marie-Kim St-Pierre (1) – Micaël Carrier (1) – Julie Savage (1) – Mathieu Morissette (3) – Marie-Ève Tremblay (1)
Université Laval CRCHU de Québec, Université Laval, Quebec, Canada (1) – Faculté de Sciences et Ingénerie, Universtié Sorbonne, Paris, France (2) – IUCPQ, IUCPQ, Departement de médicine, Université Laval, Quebec, Canada (3)


According to World Health Organization, in 2015, there were 1.1 billion smokers worldwide. Smoking is responsible for 7 million deaths per year and represents an important risk factor for several diseases. Animal studies have shown that smoking causes increased levels of inflammatory markers and oxidative stress in several organs including the brain. Microglia are the resident immune cells of the brain. They are required for the proper functioning of the brain and are equipped with a myriad of receptors that allow them to monitor their environment, recognize damage, eliminate cells and react to insult. A lesser known function of microglia is their role in plasticity. They can promote the growth or directly eliminate synapses by phagocytosis, making them active modifiers of the neuronal network. Microglial functions are tightly regulated by their environment, suggesting possible effect of the proinflammatory condition caused by cigarette smoke. Using a model of sub-chronic cigarette smoke exposure, this project aims to study the effect cigarette smoke has on hippocampal microglia of the dentate gyrus (DG) and the CA1 radiatum. The hippocampus contains one of the two known neurogenic niches, the polymorphic layer of the dentate gyrus. Newborn neurons are sensitive to homeostatic disruptions, which have a negative impact on their survival. Microglia are also responsible of the elimination of dying newborn neurons by phagocytosis, rendering the DG a suitable region to study changes in microglial activity. The radiatum contains a high number of synapses and becoming a relevant region to study microglia-synapse interactions. With the use of immunohistochemistry, we have studied microglial density and morphology in the DG and CA1 radiatum in ventral hippocampus. With the use of a putative marker for dark microglia we have detected an increased number of positive cells in the smoking mice. Dark microglia are a subtype of microglia that show ultrastructural signs of oxidative stress and an increased phagocytic activity. Additionally, with the use array tomography and scanning electron microscopy, we are characterizing the ultrastructural changes in microglial morphology, phagocytic activity and interactions with synaptic elements in the polymorphic layer of the DG.