A proposed pathological model in the hippocampus of subjects with schizophrenia.
1. The hippocampal formation plays an important role in the normal functioning of the brain, being implicated in cognition and sensory gating, both of which are affected in schizophrenia. The hippocampal formation receives information from the association cortices, which is processed by glutamatergic transmission within the hippocampus. Dopamine, noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine and GABA, all of which have been proposed to play a role in the neurobiology of schizophrenia, can affect this transmission. 2. The advent of the 'atypical' antipsychotics, with their broad pharmacological spectra and improved therapeutic outcome, has revitalized research into neurotransmitter dysfunction other than that of dopamine. In particular, there has been interest in the serotonergic and cholinergic systems within the hippocampal formation because these are two of the transmitter systems targeted by clozapine and olanzapine. 3. From the study of these systems, using tissue obtained postmortem from subjects with schizophrenia, we propose that there is a hyperserotonergic state in the hippocampal formation of some subjects with schizophrenia caused by a conformational change in the 5-HT transporter. The model we propose allows us to construct further studies that will test the consequences of such a hyperserotonergic state in the hippocampal formation. This model has the potential to open new avenues in schizophrenia research.
Scarr
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Rebecca L Cooper Research Laboratories, Division of Molecular Schizophrenia, The Mental Health Research Institute of Victoria, Parkville, Australia. E.Scarr@papyrus.mhri.edu.au
Copolov
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DL
Dean
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D002352:Carrier Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008959:Models, Neurological; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D011985:Receptors, Serotonin; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human