The role of glia in neurological disease

Abstract

Glial cells form a network in the central nervous system to support neurons and interact with them. The glia consist essentially of astrocytes that help with the nutrition of neurons and react in some cases of injury, oligodendrocytes that produce myelin, and microglia that are derived from the haemopoietic system and are concerned with the immunological defense of the nervous system. Experimental allergic encephalomyelitis is an animal model of multiple sclerosis, characterized by infiltrates of T cells and demyelinisation. It is produced in genetically susceptible rats (DA-Dark Agouti) by inoculation of foreign protein. Other non-susceptible rats (AO-Albino Oxford) react by producing cellular infiltrates, but this disappears by apoptosis without clinical manifestation of the disease. In this study, OX-42 antibodies were used to identify microglia, and GFAP for astrocytes, in the cellular infiltrates in the lumbar spinal cord and the brainstem 10, 14, and 21 days after inoculation of myelin basic protein. There are cellular infiltrates in both DA and AO groups 10 days after inoculation, and at 14th day the cells are even more numerous in the DA. Obvious astrocytosis is evident in the DA at 10th, 14th and 21st days, but less in the AO. Microgliosis is pronounced in both strains at 10th day. At 14th day, it disappeared in the DA, but persisted in the AO. We propose the hypothesis that the infiltrates are dispersed by microglial activity, which persists in the AO and prevents astrocytosis. In the DA, the transitory microgliosis allows astrocytosis, demyelinisation due to oligodendrocytic lesions, and clinical disease. Schizophrenia is associated with glial changes in the cerebral cortex. We have studied astrocytes and microglia in the association cortex of chronic schizophrenics and non-schizophrenic controls. The number of astrocytes does not vary between schizophrenics and controls, but microglia increased. Therefore, it can be concluded that there is cortical microgliosis in schizophrenics that could be a response to a lesion early in life, with a protective function for neighboring neurons. In adults, these microglia might serve to maintain modified cortical microcircuitry. We propose that in an animal model and also in human diseases, microglia play a key functional role in the integration of glial and neuronal activity. They protect the nervous system against external aggression, and prevent the development of serious lesions of other glia and of neurons.