Microglia and Astrocytes

Importantly, over the past decade it has been demonstrated that chemokines and chemokine receptors are not restricted to leukocytes. In the brain, chemokine receptors are not only found in microglia and astrocytes but also in oligodendrocytes, neurons, and along the brain microvasculature. In this chapter, we will focus on the functions of chemokine receptors expressed by resident CNS cells during physiologic and inflammatory conditions. 

The CNS also contains resident cells that are responsible for the innate immune response. The main cell types responsible for this function are microglia and astrocytes. 

Since TNFa and IL-6 are also important mediators in inflammatory responses, some work has also been done to investigate whether adrenoreceptors activation influences the production and release of these cytokines. TNFa, acting via two different receptors, p55 and p75, can present deleterious or protective effects in the CNS. There, it can be produced by microglia and astrocytes (Lucas et al., 2006). IL-6 has many functions in the CNS (see (Van Wagoner and Benveniste, 1999)). 

Noradrenergic depletion in AD transgenic animals showed an increase in the plaque number and plaque area as well as to an increase in the number of activated microglia and astrocytes (Heneka et al., 2006) (Kalinin et al., 2007). 

There are several reports concerning the participation of microglia and astrocyte-derived neurotrophic factors and inflammatory cytokines in neuropathic pain (Coull et al., 2005 Inoue et al., 2007 Scholz and Woolf, 2007). TNF-o was upregulated in the PNS and CNS after nerve injury, and contributed to neuropathic pain (Scholz and Woolf, 2007). The p38 MAP kinase was activated by TNF-a after nerve injury, and elicited neuropathic pain (Jin et al., 2003 Schafers et al., 2003). These findings were confirmed by studies using neutralizing antibody for TNF-a and p38 MAP kinase inhibitor (Schafers et al., 2003). A local injection of recombinant TNF-a elicited neuropathic-like pain (Wei et al., 2007). These reports indicate that TNF-a signaling has a critical role in the development... 

Fig. 1. Peripheral and central mechanism of neuropathic pain caused by vincristine. The upper diagram shows the effect of vincristine on the peripheral nervous system (comprising Schwann cells and the dorsal root ganglion (DRG)) and the involvement of interleukin (IL)-6 derived from infiltrating macrophages in neuropathic pain caused by vincristine. The lower diagram shows the effect of vincristine on the central nervous system, and the involvement of tumor necrosis factor-a (TNF-a) derived from activated microglia and astrocytes in neuropathic pain caused by vincristine.

Savchenko VL, McKanna JA, Nikonenko JK, Skibo GG (2000) Microglia and astrocytes in the adult rat brain comparative immunocytochemical analysis demonstrates the efficacy of lipocortin 1 immunoreactivity. Neuroscience 96 195-203. 

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