Abstract
In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function in neurotransmission since the astrocyte activated by neurotransmitters produces gliotransmitters that negatively feedback to the presynapse. It is hypothesized that in schizophrenia nonfunctional astrocytic receptors cannot be activated, thus losing their modulating function. This causes a generalization of information processing in the neuronal networks such that the brain is unable to distinguish between subjects and objects in the environment. Delusions, hallucinations and cognitive impairment occur on the behavioral level. In a model of a cholinergic tripartite synapse, it is shown that glial binding proteins modify neurotransmission by occupancy with cognate neurotransmitters temporarily turning off neurotransmission on the presynapse. Most recently, glial binding proteins have been engineered. It is proposed that the substitution of glial binding proteins may balance synaptic information processing in schizophrenia since these proteins exert a modulatory function comparable to functional astrocytic receptors. Rap- id technical developments may enable this novel treatment approach in schizophrenia.
Highlights
Schizophrenia is a worldwide neuropsychiatric disorder with about 1% incidence
The hypothetical model presented here focuses on non-functional astrocytic receptors that cause a total unbalance of synaptic information processing, since the glial modifying function is lost
A binding protein was engineered which contains the ligand recognition properties of the 5-Hydroxytryptamine 3 receptor (5-HT3R). This ligand-binding pocket of the 5-Hydroxytryptamine receptor (5-HT3R) was engineered by mutation in the original scaffold of the Aplysia california acetylcholine-binding protein (AchBP)
Summary
Schizophrenia is a worldwide neuropsychiatric disorder with about 1% incidence. The core symptoms are delusions, hallucinations and cognitive impairment. As experimentally indicated [7], an unconstrained flux of neurotransmission in synapses may cause a generalization of information processing in the brain, since oligodendrocyte-axonic information transfer is affected [8]. Such severe impairment of brain functions makes the patient incapable of distinguishing between himself and the others. The hypothetical model presented here focuses on non-functional astrocytic receptors that cause a total unbalance of synaptic information processing, since the glial modifying function is lost. I propose that engineered glial binding proteins may exert a balancing effect, modifying synaptic information processing and structuring cognitive operations in the neuronal networks
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