**2.2. Neuro-glial interactions**

Microglia activation may be beneficial, deleterious or neutral [8, 9]. Neurons express cell surface glycoproteins (CD22, CD47, CD200, and NCAM) to prevent microglia activation [10, 19]. A relationship between the nervous and immune system has been studied this past decade. Indeed, glial cells (microglia and astrocytes) not only perform supportive and nutritive roles for neurons, but also serve to defend the CNS. On the other hand, excessive and prolonged glial cell activation may result in more severe and chronic neuronal damage, leading to neuroinflammation and neurodegeneration [11, 13].

Neurons are able to control microglia with two types of signals: "On" or "Off" [20]. Off signals (TGF-β, CD22, CX3CL1, neurotransmitters, and CD20) are found in healthy conditions to maintain homeostasis and also restrict microglial activities under inflammatory conditions to prevent damage to healthy tissue. Conversely, "On" signals [CCL21, CXCL10, and MMP3 (from apoptotic neurons)] are produced by damaged and impaired neurons to activate microglia (pro- or anti-inflammatory) [21].
