Astrocytes: Adhesion Molecules and Immunomodulation

Protection of neurons, as well as maintenance of their general homeostasis and trophic support is performed by glial cells. Astrocytes, the most abundant glial cell, increase in size and number evolutionarily such that invertebrates contain fewer small astrocytes, while humans have large multi-branched astrocytes that constitute up to 60% of central nervous system (CNS) cells. Astrocytes provide neurotrophic support, induce synaptogenesis and are integral for maintenance and pruning of synapses in the adult. Following injury and in disease, their ability to respond to, and initiate initial responses to injury/disease is increasingly apparent - with alterations in function that disrupt the internal milieu of the CNS, which ultimately may lead to deficits in neuronal health and functioning. Additionally, it seems certain astrocytes serve as liaison between the CNS and the peripheral immune system. In this role, astrocytes function much like macrophages, capable of phagocytosis and production of antigens to recruit additional immune cells. Aside from up-regulation of traditional immune modulators after injury, astrocytes express many adhesion molecules such as VCAM1, NCAM1 and ICAM1, which represent potential drug targets in a number of CNS inflammatory diseases. These molecules may facilitate astrocyte-lymphocyte interactions ultimately aiding recruitment of immune cells into the CNS. Due to their immense numbers and widespread presence in the brain, combined with their capacity for rapid proliferation, astrocytes are well-positioned as gate-keepers of CNS immune responses. Beyond roles in immune and inflammatory activities, astrocytes also affect a complex array of neural functions and behaviours like mood, sleep, and pain, as well as altering the CNS capacity for recovery following injury/illness. Further, their complex effects on synaptic function suggest that astrocytes are key players in neuropsychiatric and neurodegenerative diseases.