Possible role of glia in cognitive impairment in schizophrenia

Cognitive impairment is a core disorder of the schizophrenia syndrome. Based on glial-neuronal interactions, a pathophysiological model is proposed that could be explanatory for cognitive impairment in schizophrenia. The model consists of three main hypotheses concerning the pathophysiology in tripartite synapses, oligodendrocyte-axonic interactions, and in the glial networks (astrocytic syncytium). In tripartite synapses nonfunctional astrocytic receptors may cause an unconstrained synaptic information flux, since they cannot be occupied by neurotransmitters (NTs). Therefore, a generalization of information processing may occur in the brain causing hallucinations, delusions, and thought disorder. If the oligodendrocyte-axonic system decomposes, the brain is unable to process information in qualitative domains or categories. This may lead to severe incoherence phenomena such as thought disorder. Supposing that in the astrocytic syncytium gap junctions (g.js) normally form plaques functioning as memory devices, loss of function of g.j. may also cause cognitive impairment, since the syncytium decomposes and g.j. plaques cannot be generated. These hypotheses are experimentally testable. Finally, the problem of treatment of patients with schizophrenia is discussed, in case the presented model of schizophrenia might be verified.