Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy.
In the last 10 years, structural, molecular and functional changes in glial cells have become a major focus of interest in the search for the neurobiological foundations of schizophrenia. While neuronal degeneration, as seen in typical degenerative brain diseases, cannot be found in post-mortem brains of psychotic disorders called 'schizophrenia', many studies show abnormalities in the connecting elements between the nerve cell bodies (synapses, dendrites and axons) and in all three types of glial cells. There is accumulating evidence of reduced numbers of oligodendrocytes and altered gene expression of myelin/oligodendrocyte-related genes that might explain white matter abnormalities and disturbed inter- and intra-hemispheric connectivity, which have frequently been described in schizophrenia. Earlier reports of increased astrocyte densities as a sign of gliosis could not be confirmed by later studies; however, the expression of several astrocyte-related genes is abnormal. Since astrocytes play a key role in the synaptic metabolism of glutamate and monamines, astrocyte dysfunction may well be related to the current transmitter theories of schizophrenia. Results in increased densities of microglial cells, which act as the main cells for immune defence in the brain, are more controversial. There are, however, higher microglial cell numbers in psychotic patients dying from suicide, and several studies reported altered expression of microglia-related surface markers in schizophrenia, suggesting that immunological/inflammatory factors may be relevant for the pathophysiology of psychosis. Searches for future therapeutic options should aim at compensating disturbed functions of oligodendrocytes, astrocytes and microglial cells, by which at least some aspects of the pathophysiology of the very inhomogeneous clinical syndrome of schizophrenia might be explained.
Bernstein
Hans-Gert
HG
Department of Psychiatry, Otto von Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany. hans-gert.bernstein@med.ovgu.de
Steiner
Johann
J
Bogerts
Bernhard
B
D000818:Animals; D001921:Brain / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D009457:Neuroglia / Q000145:classification / Q000473:pathology / Q000502:physiology*; D012559:Schizophrenia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy