The role of astrocytes and complement system in neural plasticity.
In neurotrauma, brain ischemia or neurodegenerative diseases, astrocytes become reactive (which is known as reactive gliosis) and this is accompanied by an altered expression of many genes. Two cellular hallmarks of reactive gliosis are hypertrophy of astrocyte processes and the upregulation of the part of the cytoskeleton known as intermediate filaments, which are composed of nestin, vimentin, and GFAP. Our aim has been to better understand the function of reactive astrocytes in CNS diseases. Using mice deficient for astrocyte intermediate filaments (GFAP(-/-)Vim(-/-)), we were able to attenuate reactive gliosis and slow down the healing process after neurotrauma. We demonstrated the key role of reactive astrocytes in neurotrauma-at an early stage after neurotrauma, reactive astrocytes have a neuroprotective effect; at a later stage, they facilitate the formation of posttraumatic glial scars and inhibit CNS regeneration, specifically, they seem to compromise neural graft survival and integration, reduce the extent of synaptic regeneration, inhibit neurogenesis in the old age, and inhibit regeneration of severed CNS axons. We propose that reactive astrocytes are the future target for the therapeutic strategies promoting regeneration and plasticity in the brain and spinal cord in various disease conditions. Through its involvement in inflammation, opsonization, and cytolysis, complement protects against infectious agents. Although most of the complement proteins are synthesized in CNS, the role of the complement system in the normal or ischemic CNS remains unclear. Complement activiation in the CNS has been generally considered as contributing to tissue damage. However, growing body of evidence suggests that complement may be a physiological neuroprotective mechanism as well as it may participate in maintenance and repair of the adult brain.
Pekny
Milos
M
Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience and Rehabilitation, Institute for Neuroscience and Physiology at Sahlgrenska Academy Göteborg University, 405 30 Göteborg, Sweden.
Wilhelmsson
Ulrika
U
Bogestål
Yalda Rahpeymai
YR
Pekna
Marcela
M
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D020196:Trauma, Nervous System / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein; D003165:Complement System Proteins