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Possible effects of synaptic imbalances on oligodendrocyte-axonic interactions in schizophrenia: a hypothetical model.

Mitterauer BJ, Kofler-Westergren B - Front Psychiatry (2011)

Bottom Line: The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination.It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes.Demyelination decomposes the oligodendrocyte-axonic system making it incapable to generate categories of information.

View Article: PubMed Central - PubMed

Affiliation: Volitronics - Institute for Basic Research, Psychopathology and Brain Philosophy Wals/Salzburg, Austria.

ABSTRACT
A model of glial-neuronal interactions is proposed that could be explanatory for the demyelination identified in brains with schizophrenia. It is based on two hypotheses: (1) that glia-neuron systems are functionally viable and important for normal brain function, and (2) that disruption of this postulated function disturbs the glial categorization function, as shown by formal analysis. According to this model, in schizophrenia receptors on astrocytes in glial-neuronal synaptic units are not functional, loosing their modulatory influence on synaptic neurotransmission. Hence, an unconstrained neurotransmission flux occurs that hyperactivates the axon and floods the cognate receptors of neurotransmitters on oligodendrocytes. The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination. In parallel, an increasing impairment of axons may disconnect neuronal networks. It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes. Demyelination decomposes the oligodendrocyte-axonic system making it incapable to generate categories of information. This incoherence may be responsible for symptoms of disorganization in schizophrenia, such as thought disorder, inappropriate affect and incommunicable motor behavior. In parallel, the loss of oligodendrocytes affects gap junctions in the panglial syncytium, presumably responsible for memory impairment in schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the excess of neurotransmitters that may cause a loss of oligodendrocytes and decomposition or disconnection of oligodendrocyte–axonic interactions and neuronal networks. A synaptic neurotransmitter (NT) excess hyperexcites the axon and floods the cognate receptors (R) on the oligodendrocyte (Oc). In parallel, a non-synaptic ATP excess occurs, also flooding R. This flooding of NT and ATP exerts a toxic effect on the Oc, leading to its decay. These mechanisms may be responsible for the decomposition of oligodendrocyte–axonic interactions and the disconnection of neuronal networks.
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Figure 9: Schematic diagram of the excess of neurotransmitters that may cause a loss of oligodendrocytes and decomposition or disconnection of oligodendrocyte–axonic interactions and neuronal networks. A synaptic neurotransmitter (NT) excess hyperexcites the axon and floods the cognate receptors (R) on the oligodendrocyte (Oc). In parallel, a non-synaptic ATP excess occurs, also flooding R. This flooding of NT and ATP exerts a toxic effect on the Oc, leading to its decay. These mechanisms may be responsible for the decomposition of oligodendrocyte–axonic interactions and the disconnection of neuronal networks.

Mentions: In line with the presented synaptic model of the pathophysiology of schizophrenia, an unconstrained flux of neurotransmitters occurs. This may hold for all the various neurotransmitter types. This unconstrained flux of neurotransmitters may affect oligodendrocytes either by flooding of their cognate receptors on oligodendrocytes, exerting a toxic Ca2+ influx, or via a hyperactivation of axons with an excess of axonic ATP production and a consequent toxic effect on oligodendrocytes (Figure 9). In addition, ATP released from axons cannot activate astrocytic receptors, since they do not function. Therefore, a stimulation of myelination by mature oligodendrocytes is not possible. These pathological mechanisms may cause demyelination, as observed in brains with schizophrenia (Skelly et al., 2008; Takahashi et al., 2010). Note, although decreased expression of oligodendrocyte-related genes has been identified (Höstad et al., 2009), it seems implausible that genetics alone could account for demyelination in schizophrenia (Fields, 2009).


Possible effects of synaptic imbalances on oligodendrocyte-axonic interactions in schizophrenia: a hypothetical model.

Mitterauer BJ, Kofler-Westergren B - Front Psychiatry (2011)

Schematic diagram of the excess of neurotransmitters that may cause a loss of oligodendrocytes and decomposition or disconnection of oligodendrocyte–axonic interactions and neuronal networks. A synaptic neurotransmitter (NT) excess hyperexcites the axon and floods the cognate receptors (R) on the oligodendrocyte (Oc). In parallel, a non-synaptic ATP excess occurs, also flooding R. This flooding of NT and ATP exerts a toxic effect on the Oc, leading to its decay. These mechanisms may be responsible for the decomposition of oligodendrocyte–axonic interactions and the disconnection of neuronal networks.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3102422&req=5

Figure 9: Schematic diagram of the excess of neurotransmitters that may cause a loss of oligodendrocytes and decomposition or disconnection of oligodendrocyte–axonic interactions and neuronal networks. A synaptic neurotransmitter (NT) excess hyperexcites the axon and floods the cognate receptors (R) on the oligodendrocyte (Oc). In parallel, a non-synaptic ATP excess occurs, also flooding R. This flooding of NT and ATP exerts a toxic effect on the Oc, leading to its decay. These mechanisms may be responsible for the decomposition of oligodendrocyte–axonic interactions and the disconnection of neuronal networks.
Mentions: In line with the presented synaptic model of the pathophysiology of schizophrenia, an unconstrained flux of neurotransmitters occurs. This may hold for all the various neurotransmitter types. This unconstrained flux of neurotransmitters may affect oligodendrocytes either by flooding of their cognate receptors on oligodendrocytes, exerting a toxic Ca2+ influx, or via a hyperactivation of axons with an excess of axonic ATP production and a consequent toxic effect on oligodendrocytes (Figure 9). In addition, ATP released from axons cannot activate astrocytic receptors, since they do not function. Therefore, a stimulation of myelination by mature oligodendrocytes is not possible. These pathological mechanisms may cause demyelination, as observed in brains with schizophrenia (Skelly et al., 2008; Takahashi et al., 2010). Note, although decreased expression of oligodendrocyte-related genes has been identified (Höstad et al., 2009), it seems implausible that genetics alone could account for demyelination in schizophrenia (Fields, 2009).

Bottom Line: The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination.It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes.Demyelination decomposes the oligodendrocyte-axonic system making it incapable to generate categories of information.

View Article: PubMed Central - PubMed

Affiliation: Volitronics - Institute for Basic Research, Psychopathology and Brain Philosophy Wals/Salzburg, Austria.

ABSTRACT
A model of glial-neuronal interactions is proposed that could be explanatory for the demyelination identified in brains with schizophrenia. It is based on two hypotheses: (1) that glia-neuron systems are functionally viable and important for normal brain function, and (2) that disruption of this postulated function disturbs the glial categorization function, as shown by formal analysis. According to this model, in schizophrenia receptors on astrocytes in glial-neuronal synaptic units are not functional, loosing their modulatory influence on synaptic neurotransmission. Hence, an unconstrained neurotransmission flux occurs that hyperactivates the axon and floods the cognate receptors of neurotransmitters on oligodendrocytes. The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination. In parallel, an increasing impairment of axons may disconnect neuronal networks. It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes. Demyelination decomposes the oligodendrocyte-axonic system making it incapable to generate categories of information. This incoherence may be responsible for symptoms of disorganization in schizophrenia, such as thought disorder, inappropriate affect and incommunicable motor behavior. In parallel, the loss of oligodendrocytes affects gap junctions in the panglial syncytium, presumably responsible for memory impairment in schizophrenia.

No MeSH data available.


Related in: MedlinePlus