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DOI: 10.1055/s-2003-40502
Die Bedeutung von Interneuronen bei affektiven und schizophrenen Erkrankungen
The Importance of Interneurons in Schizophrenic and Affective DisordersPublication History
Publication Date:
08 July 2003 (online)
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Zusammenfassung
Schizophrene und affektive Psychosen weisen pathomorphologische Veränderungen mit frontotemporalem Schwerpunkt auf. Die im präfrontalen Kortex beobachtete Volumenreduktion bei schizophrenen Patienten ist bei relativ erhöhter Zelldichte auf eine Neuropilreduktion zurückzuführen. Zusammen mit einer verminderten Expression synaptischer Proteine ist dies ein Hinweis auf eine gestörte neuronale Konnektivität. Für eine intakte Konnektivität sind aber auch Interneurone von großer Bedeutung. Bei schizophrenen und affektiven Psychosen sind GABA-erge Interneurone vermindert. Eine gestörte Verschaltung des glutamatergen, GABA-ergen und dopaminergen Systems könnten in Kombination mit der reduzierten Zahl von Interneuronen das Korrelat für ein defizientes neuronales Netzwerk sein, welches unter exogenen Faktoren psychotische Symptome generiert. Reelin bzw. sein Pathway stellen Kandidatenmoleküle dar, deren Fehlregulation wesentliche Merkmale des dysfunktionellen Netzwerkes bei der Schizophrenie erklären.
Abstract
In brains of patients with schizophrenic and affective disorders pathomorphological changes have been shown focussing in frontal and temporal cortex. The volume reduction in prefrontal cortex of schizophrenic patients is hypothesized to be based on a reduction of neuropil. A decrease of synaptic proteins and a decrease of dendritic spines of pyramidal cells can additionally be the origin of disconnections of neurons. Affection of the glutamatergic, GABA-ergic and dopaminergic system and reduction of interneurons could be the correlate of a deficient neuronal network which might be combined with exogen factors generate psychotic symptoms. Reelin and associated proteins are candidate molecules. Their dysregulation might explain essential features of the dysfunctional network of schizophrenia.
Literatur
- 1 Hopkins R, Lewis S. Structural imaging finding and macroscopic pathology. In: Harrison PJ, Roberts GW (Hrsg). The neuropathology of schizophrenia - Progress and Interpretation. Oxford: University Press 2000: 5-56
- 2 Vogeley K, Falkai P. The dysconnectivity hypothesis of schizophrenia. Neurology Psychiatry Brain Research. 1998; 6 113-122
- 3 Amaral D G. The anatomical organization of the central nervous system. In: Kandel ER, Schwartz JH, Jessel TM. Principles of neural science. New York, McGraw-Hill 2000: 317-336
- 4 Lewis D A. The organization of the cortical circuitry. In: Harrison PJ, Roberts GW (Hrsg). The neuropathology of schizophrenia - Progress and Interpretation Oxford: University Press 2000: 235-256
- 5 Soares J C, Mann J J. The anatomy of mood disorders - review of structural neuroimaging studies. Biol Psychiatry. 1997; 41 86-106
- 6 Benes F M, Vincent S L, Todtenkopf M. The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenics and bipolar subjects. Biol Psychiatry. 2001; 50 395-406
- 7 Rajkowska G. Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry. 2000; 48 766-777
- 8 McCarley R W, Wible C G, Frumin M, Hirayasu Y, Levitt J J, Fischer I A, Shenton M E. MRI anatomy of schizophrenia. Biol Psychiatry. 1999; 45 1099-1119
- 9 Selemon L D, Rajkowska G, Goldman-Rakic P S. Abnormally high neuronal density in the schizophrenic cortex: a morphometric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry. 1995; 52 805-818
- 10 Falkai P, Bogerts B. Cell loss in the hippocampus of schizophrenics. Eur Arch Psych Neurol Sci. 1986; 236 154-161
- 11 Benes F M, McSparren J, Bird E D, Vincent S L, SanGiovanni J P. Deficits in small interneurons in prefrontal and anterior cingulate cortex of schizophrenic and schizoaffective patients. Arch Gen Psychiatry. 1991; 48 996-1001
- 12 Benes F M, Kwok S W, Vincent S L, Todtenkopf M S. A reduction of nonpyramidal cells in sector CA2 of schizophrenics and manic depressives. Biol Psychiatry. 1998; 44 88-97
- 13 Akbarian S, Kim J J, Potkin S G, Hagman J O, Tafazzoli A, Bunney W E Jr, Jones E G. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry. 1995; 52 258-266
- 14 Rajkowska G, Selemon L D, Goldman-Rakic P S. Neuronal and glial soma size in the prefrontal cortex: a post-mortem study of schizophrenics and Huntington's disease. Arch Gen Psychiatry. 1998; 55 215-224
- 15 Selemon L D, Rajkowska G, Goldman-Rakic P S. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: Application of a 3-dimensional stereologic counting method. J Comp Neurol. 1998; 392 402-412
- 16 Selemon L D, Goldman-Rakic P S. The reduced neuropil hypothesis: A circuit based model of schizophrenia. Biol Psychiatry. 1999; 45 17-25
- 17 Garey L J, Ong W Y, Patel T S, Kanani M, Davis A, Mortimer A M, Barnes T RE, Hirsch S R. Reduction dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry. 1998; 65 446-453
- 18 Glantz L A, Lewis D A. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry. 2000; 57 65-73
- 19 Honer W G, Young C, Falkai P. Synaptic pathology. In: Harrison PJ, Roberts GW (Hrsg). The neuropathology of schizophrenia - Progress and Interpretation. Oxford: University Press 2000: 105-136
- 20 Fatemi S H, Earle J A, Stary J M, Lee S, Sedgewick J. Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Neuroreport. 2001; 12 3257-3262
- 21 Eastwood S L, Harrison P J. Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull. 2001; 55 569-578
- 22 Benes F M. Emerging principles of altered neural circuitry in schizophrenia. Brain Research Reviews. 2000; 31 251-269
- 23 Bird E D, Spokes E GS, Iversen L L. Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia. Brain. 1979; 102 347-360
- 24 Simpson M D, Slater P, Deakin J F, Ryoston M C, Skan W J. Reduced GABA uptake sites in the temporal lobe in schizophrenia. Neurosci Lett. 1989; 107 211-215
- 25 Reynolds G P, Czudek C, Andrews H. Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. Biol Psychiatry. 1990; 27 1038-1044
- 26 Beasley C L, Reynolds G P. Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics. Schizophr Res. 1996; 24 349-355
- 27 Benes F M, Vincent S L, Alsterberg G, Bird E D, SanGiovanni J-P. Increased GABA receptor binding in supragranular layers of schizophrenic cingulate cortex. J Neurosci. 1992; 12 924-929
- 28 Benes F M, Vincent S, Marie A, Khan Y. Upregulation of GABA-A receptor binding on neurons of the prefrontal cortex in schizophrenic subjects. Neurosci. 1996; 75 1021-1031
- 29 Benes F M, Khan Y, Vincent S L, Wickramasinghe R. Differences in the subregional and cellular distribution of GABA-A receptor binding in the hippocampal formation of schizophrenic brain. Synapse. 1996; 22 338-349
- 30 Woo T-U, Whitehead R E, Melchitzky D S, Lewis D A. A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA. 1998; 95 5341-5346
- 31 Benes F M, Majocha R, Bird E D, Marotta C A. Increased vertical axon numbers in cingulate cortex of schizophrenics. Arch Gen Psychiatry. 1987; 44 1017-1021
- 32 Benes F M, Sorensen I, Vincent S L, Bird E D, Sathi M. Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Cereb Kortex. 1992; 2 502-512
- 33 Benes F M. Cortical pathology: a new generation of quantitative microscopic studies. In: Harrison PJ, Roberts GW (Hrsg). The neuropathology of schizophrenia - Progress and Interpretation. Oxford: University Press 2000: 81-104
- 34 Benes F M, Todtenkopf M S, Taylor J B. Differential distribution of tyrosine hyxdroxylase fibers on neuronal subtypes in layer II of anterior cingulate cortex of schizophrenic brain. Synapse. 1997; 25 80-92
- 35 Benes F M, Todtenkopf M S, Logiotatos P, Williams M. Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. J Chem Neuroanat. 2000; 20 259 -269
- 36 Falkai P, Honer W G, David S, Bogerts B, Majtenyi C, Bayer T A. No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem study. Neuropathol Appl Neurobiol. 1999; 25 48-53
- 37 Guidotti A, Auta J, Davis J M, DiGieorgi Gerevini V, Dwivedi Y, Grayson D R, Impagnatiello F, Pandey G, Pesold C, Sharma R, Uzunov D, Costa E. Decrease in Reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder. Arch Gen Psychiatry. 2000; 57 1061-1069
- 38 Fatemi S H, Earle J A, McMenomy T. Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry. 2000; 5 654-663
- 39 Block W, Bayer T A, Tepest R, Traber F, Rietschel M, Muller D J, Schulze T G, Honer W G, Maier W, Schild H H, Falkai P. Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study. Neurosci Lett. 2000; 289 147-151
Dr. med. Harald Scherk
Universitätskliniken des Saarlandes, Nervenklinik und Poliklinik - Psychiatrie und Psychotherapie
66421 Homburg
Email: harald.scherk@uniklinik-saarland.de