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DOI: 10.1055/a-1149-9280
Struktur und Efferenzen der Substantia nigra pars compacta beim idiopathischen Parkinson-Syndrom
Structure and efferences of the substantia nigra pars compacta in Parkinson’s disease![](https://www.thieme-connect.de/media/fdn/202009/lookinside/thumbnails/10.1055a-1149-9280-1.jpg)
Zusammenfassung
Es besteht Konsens, dass das neuropathologische Merkmal des idiopathischen Parkinson-Syndroms (IPS) der neuronale Zellverlust der Substantia nigra pars compacta (SNc) in Verbindung mit einer Lewy-Pathologie ist. Die transsynaptische Ausbreitung der Lewy-Pathologie wird als wesentlich in der Parkinson-Pathogenese angesehen. Daher ist die Kenntnis präexistenter neuroanatomischer Verbindungen der SNc wesentlich. Wir beschreiben hier neuere tierexperimentelle Befunde zu den afferenten und efferenten Projektionen der SNc und diskutieren die Evidenz für und gegen die sequentielle transsynaptische Ausbreitung der Lewy-Pathologie in der Pathogenese des IPS.
Abstract
There is consensus that the neuropathological characteristic of Parkinson’s disease (PD) is the neuronal cell loss of the substantia nigra pars compacta (SNc) in connection with a Lewy pathology. The transsynaptic spread of Lewy pathology is considered essential in PD pathogenesis. Therefore, the knowledge of pre-existing neuroanatomical connections of the SNc is essential. We describe recent animal experiments on the afferent and efferent projections of the SNc and discuss the evidence for and against the sequential transsynaptic spread of Lewy pathology in the pathogenesis of PD.
Schlüsselwörter
idiopathisches Parkinson-Syndrom - Lewy-pathology - Substatia nigra - NeuropathologiePublication History
Received: 20 October 2020
Accepted: 24 March 2020
Article published online:
12 May 2020
© Georg Thieme Verlag KG
Stuttgart · New York
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Literatur
- 1 Greffard S, Verny M, Bonnet AM. et al. Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of Lewy-body associated neuronal loss in the substantia nigra. Arch Neurol 2006; 63: 584-588
- 2 Carlsson A, Falck B. Hillarp NA Cellular localization of brain monoamines. Acta Physiol Scand Suppl 1962; 56: 1-28
- 3 Dahlström A, Fuxe K. Evidence of the existence of monoamine-containing neurons in the central nervous system. Acta Physiol Scand Suppl 1964; 232: 1-55
- 4 Hegarty SV, Sullivan AM, O’Keeffe GW. Midbrain dopaminergic neurons: A review of the molecular circuitry that regulates their development. Developmental Biol 2013; 379: 123-138
- 5 Björklund A, Dunnett SB. Dopamine neuron systems in the brain: An update. Trends Neurosci 2007; 30: 194-202
- 6 McRitchie DA, Cartwright HR, Halliday GM. Specific A10 dopaminergic nuclei in the midbrain degenerate in Parkinson’s disease. Exp Neurol 1997; 144: 202-213
- 7 Lynd-Balta E, Haber SN. The organization of midbrain projections to the ventral striatum in the primate. Neuroscience 1994; 59: 609-623
- 8 Lynd-Balta E, Haber SN. The organization of midbrain projections to the striatum in the primate: Sensorimotor-related striatum versus ventral striatum. Neuroscience 1994; 59: 625-640
- 9 Gerfen CR, Herkenham H, Thibault J. The nigrostriatal mosaic: Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 1987; 7: 3915-3934
- 10 Brimblecombe KR, Cragg SJ. The striosome and matrix compartiments of the striatum: A path through the labyrinth from neurochemistry toward function. ACS Chem Neurosci 2017; 8: 235-242
- 11 Smith JB, Klug JR, Ross DL. et al. Genetic based dissection unveils the inputs and outputs of striatal patch and matrix compartiments. Neuron 2016; 91: 1069-1084
- 12 Haber SN, Fudge JL, McFarland NR. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci 2000; 20: 2369-2382
- 13 Jellinger K. Neuropathology of sporadic Parkinson’s disease: Evaluation and changes of concepts. Mov Dis 2012; 27: 8-30
- 14 Prensa L, Parent A. The nigrostriatal pathway in the rat: A single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments. J Neurosci 2001; 21: 7247-7260
- 15 Matsuda W, Furuta T, Nakamura KC. et al. Single nigrostriatal dopaminergic neurons from widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci 2009; 29: 444-453
- 16 Höglinger GU, Alvarez-Fischer D, Arias-Carrion O. et al. A new dopaminergic nigro-olfactory projection. Acta Neuropathol 2015; 130: 333-348
- 17 Anselmi L, Toti L, Bove C. et al. A nigro-vagal pathway controls gastric motility and is affected in a rat model of parkinsonism. Gastroenterology 2017; 153: 1581-1593
- 18 Wang Z-Y, Liau H, Cai - Q-Q. et al. No direct projection is observed from the substantia nigra to the dorsal vagus complex in the rat. J Park Dis 2014; 4: 375-383
- 19 Almada RC, Genewsky AJ, Heinz DE. et al. Stimulation of the nigrotectal pathway at the level of the superior colliculus reduces threat recognition and causes a shift from avoidance to approach behavior. Front Neural Circuits 2018; 12: 1-9
- 20 Perez-Fernandez J, Kardamakis AA, Suzuki DG. et al. Direct dopaminergic projections from the SNc modulate visuomotor transformation in the lamprey tectum. Neuron 2017; 96: 910-924
- 21 Rossi MA, Haofang EL, Dongye L. et al. A GABAergic nigrotectal pathway for coordination of drinking behaviour. Nat Neurosci 2016; 19: 742-748
- 22 Hormigo S, Lopez DE, Cardoso A. et al. Direct and indirect nigrofugal projections to the nucleus reticularis pontis caudalis mediate in the motor execution of the acoustic startle reflex. Brain Structure Function 2018; 223: 2733-2751
- 23 Cebrian C, Prensa L. Basal ganglia and thalamic input from neurons located within the ventral tier cell clusters region of the substantia nigra pars compacta in the rat. J Comp Neurol 2010; 518: 1283-1300
- 24 Freeman A, Ciliax B, Bakay R. et al. Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models. Ann Neurol 2001; 50: 321-329
- 25 Dirkx MF, den Ouden HEM, Aarts E. et al. Dopamine controls pakinson’s tremor by inhibiting the cerebellar thalamus. Brain 2017; 140: 721-734
- 26 Sakai S, Grofova I, Bruce K. Nigrothalamic projections and nigrothalamocortical pathway to the medial agranular cortex in the rat: Single- and double labeling light and electron microscopic studies. J Comp Neurol 1998; 391: 506-525
- 27 Tanibuchi I, Kitano H, Jinnai K. Substantia nigra output to prefrontal cortex via thalamus in monkeys. I. Electrophysiological identification of thalamic relay neurons. J Neurophysiol 2009; 102: 2933-2945
- 28 Kirouc GJ, Li S, Mabrouk G. GABAergic projection from the ventral tegmental area and substantia nigra to the periaqueductal gray region and the dorsal raphe nucleus. J Comp Neurol 2004; 469: 170-184
- 29 French IT, Muthusamy KA. A review of the pedunculopontine nucleus in Parkinson’s disease. Front Aging Neurosci 2018; 10: 1-15
- 30 Freundlieb N, Francois C, Tande D. et al. Dopaminergic substantia nigra neurons project topographically organized to the subventricular zone and stimulate precursor cell proliferation in aged primates. J Neurosci 2006; 26: 2321-2325
- 31 Bostan AC, Strick PL. The basal ganglia and the cerebellum: Nodes in an integrated network. Nat Rev Neurosci 2018; 19: 338-350
- 32 Parent A, Lavoie B, Smith Y. et al. The dopaminergic nigropallidal projection in primates: Distinct cellular origin and relative sparing in MPTP-treated monkeys. Adv Neurol 1990; 53: 111-116
- 33 Dickson DW, Braak H, Duda JE. et al. Neuropathological assessment of Parkinson’s disease: Refining the diagnostic criteria. Lancet Neurol 2009; 8: 1150-1157
- 34 Braak H, Sandmann-Keil D, Gai W. et al. Extensive axonal Lewy-neurites in Parkinson’s disease: A novel pathological feature revealed by alpha-synuclein immunocytochemistry. Neurosci Lett 1999; 265: 67-69
- 35 Spillantini MG, Schmidt ML, Lee VM. et al. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-840
- 36 Halliday GM, Leverenz JB, Schneider JS. et al. The neurobiological basis of cognitive impairment in Parkinson’s disease. Mov Disord 2014; 29: 634-650
- 37 Dauer W, Przedborski S. Parkinson’s disease: Mechanisms and models. Neuron 2003; 39: 889-909
- 38 Gibb WRG, Lees AJ. Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1991; 54: 388-396
- 39 Surmeier DJ, Sulzer D. The pathology roadmap in Parkinson disease. Prion 2013; 7: 85-91
- 40 Nemani VM, Lu W, Berge V. et al. Increased expression of alpha-Synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010; 65: 66-79
- 41 Riederer P, Berg D, Casadei N. et al. Alpha-synuclein in Parkinson’s disease: Causal or bystander? J Neural Transm 2019; 126: 815-840
- 42 Schulz-Schaeffer WJ. Neurodegeneration in Parkinson disease. Neurology 2012; 79: 2298-2299
- 43 Cheng HC, Ulane CM, Burke RE. Clinical progression in Parkinson disease and the neurobiology of axons. Ann Neurol 2010; 67: 715-725
- 44 Pasquini J, Ceravolo R, Qamhawi Z. et al. Progression of tremor in early stages of Parkinson’s disease: A clinical and neuroimaging study. Brain 2018; 141: 811-821
- 45 Qamhawi Z, Towey D, Shah B. et al. Clinical correlates of raphe serotonergic dysfunction in early Parkinson’s disease. Brain 2015; 138: 2964-2973
- 46 Braak H, Del Tredici K, Rüb U. et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 2003; 24: 197-211
- 47 Braak H, Bohl JR, Müller CM. et al. Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson’s disease reconsidered. Mov Dis 2006; 21: 2042-2051
- 48 Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: A dual-hit hypothesis. Neuropathol Appl Neurobiol 2007; 33: 599-614
- 49 Halliday G, Hely M, Reid W. et al. The progression of pathology in longitudinally followed patients with Parkinson’s disease. Acta Neuropathol 2008; 115: 409-415
- 50 Kingsbury AE, Bandopadhyay R, Silveira-Moriyama L. et al. Brain stem pathology in Parkinson’s disease: An evaluation of the Braak staging model. Mov Dis 2010; 15: 2508-2015
- 51 Saito Y, Shioya A, Sano T. et al. Lewy body pathology involves the olfactory cells in Parkinson’s disease and related disorders. Mov Dis 2016; 31: 135-138
- 52 Berendse HW, Booij J, Francot CMJE. et al. Subclinical dopaminergic dysfunction in asymptomatic parkinson’s disease patients’ relatives with a decreased sense of smell. Ann Neurol 2001; 50: 34-41
- 53 Ross GW, Petrovitch H, Abbott RD. et al. Association of olfactory dysfunction with risk for future parkinson’s disease. Ann Neurol 2008; 63: 167-173
- 54 Braak H, de Vos RA, Bohl J. et al. Gastric alphy-synuclein immunorective inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 2006; 396: 67-72
- 55 Del Tredici K, Hawkes CH, Ghebremedhin E. et al. Lewy pathology in the submandibular gland of individuals with incidental Lewy body disease and sporadic Parkinson’s disease. Acta Neuropathol 2010; 119: 703-713
- 56 Minguez-Castellanos A, Chamorro CE, Escamilla-Sevilla F. et al. Do alpha-synuclein aggregates in autonomic plexuses predate Lewy body disorders?: A cohort study. Neurology 2007; 68: 2012-2018
- 57 Stokholm MG, Danielsen EH, Hamilton-Dutolt SJ. et al. Pathological alpha-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol 2016; 79: 940-949
- 58 Pan-Montijo F, Anichtchik O, Dening Y. et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One 2010; 5: e8762
- 59 Pan-Montojo F, Schwarz M, Winkler C. et al. Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice. Sci Rep 2012; 2: 898
- 60 Liu B, Fang F, Pedersen NL. et al. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology 2017; 88: 1-7
- 61 Svensson E, Horvath-Puho E, Thomsen RW. et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 2015; 78: 522-529
- 62 Holmqvist S, Chutna O, Bousset L. et al. Direct evidence of Parkinson pathology spread from the gastrointestinal tract in the brain in rats. Acta Neuropathol 2014; 128: 805-820
- 63 Ulusoy A, Musgrove RE, Rusconi R. et al. Neuron-to-neuron α-synuclein propagation in vivo is independent of neuronal injury. Acta Neuropathol Commun 2015; 3: 13
- 64 Kim S, Kwon S-H, Kam T-I. et al. Transneuronal proagation of pathologic α-synuclein from the gut to the brain models parkinson’s disease. Neuron 2019; 103: 627-641
- 65 Kordower JH, Chu Y, Hauser RA. et al. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 2008; 14: 504-507
- 66 Li J-Y, Englund E, Holton JI. et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med 2008; 14: 501-503
- 67 Recasens A, dehay B, Bove J. et al. Lewy Body Extracts from Parkinson disease brains trigger α-synuclein pathology and neurodegeneration in mice and monkeys. Ann Neurol 2014; 75: 351-362
- 68 Attems J, Jellinger KA. The dorsal motor nucleus of the vagus is not an obligatory trigger site of parkinson’s disease. Neuropathol Appl Neurobiol 2008; 34: 466-467
- 69 Kalaitzakis ME, Graeber MB, Gentleman SM. et al. The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson’s disease: A critical analysis of alpha-synuclein staging. Neuropathol Appl Neurobiol 2008; 34: 284-295
- 70 Surmeier DJ, Obeso JA, Halliday GM. Parkinson’s disease is not simply a prion disorder. J Neurisci 2017; 37: 9799-9807
- 71 Burke RE, Dauer WT, Vonsattel JPG. A critical evaluation of the Braak staging scheme for Parkinson’s disease. Ann Neurol 2008; 64: 485-491
- 72 Miyakawa S, Ogino M, Funabe S. et al. Lewy body pathology in a patient with a homozygotous Parkin deletion. Mov Dis 2013; 28: 388-391
- 73 Dijkstra AA, Voorn P, Berendse HW. et al. Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson’s disease. Mov Dis 2014; 29: 1244-1251
- 74 Milber JM, Noorigian JV, Morley JF. et al. Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease. Neurology 2012; 79: 2307-2314
- 75 Wakabayashi K, Takahashi H, Takeda S. et al. Parkinson’s disease: The presence of Lewy bodies in Auerbach’s and Meissner’s plexuses. Acta Neuropathol 1988; 76 (03) : 217-221
- 76 Wakabayashi K, Toyoshima Y, Awamori K. et al. Restricted occurrence of Lewy bodies in the dorsal vagal nucleus in a patient with late-onset parkinsonism. J Neurol Sci 1999; Jun 1;. 165 (02) : 188-191
- 77 Böttner M, Zorenkov D, Hellwig I. et al. Expression pattern and localization of alpha-synuclein in the human enteric nervous system. Neurobiol Dis 2012; 48: 474-480
- 78 Visanji NP, Marras C, Kern DS. et al. Colonic mucosal a-synuclein lacks specificity as a biomarker for Parkinson disease. Neurology 2015; 84: 609-616
- 79 Annerino DM, Arshad S, Taylor GM. et al. Parkinson’s disease is not associated with gastrointestinal myenteric ganglion neuron loss. Acta Neuropathol 2012; 124: 665-680
- 80 Sung HY, Park JW, Kim JS. The frequency and severity of gastrointestinal symptoms in patients with early Parkinson’s disease. J Mov Disord 2014; 7: 7-12
- 81 Parkkinen L, Pirttila T, Alafuzoff I. Applicability of current staging/catergorization of alpha-synuclein pathology and their clinical relevance. Acta Neuropathol 2008; 115: 399-407
- 82 Killinger BA, Kordower JH. Spreading of alpha-synuclein – Relevant or epiphenomenon? J Neurochem 2019; 150: 605-611
- 83 Espay AJ, Vizcarra JA, Marsili L. et al. Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer disease. Neurology 2019; 92: 329-337
- 84 Foffani G, Obeso JA. A cortical pathogenic theory of Parkinson’s disease. Neuron 2018; 99: 1116-1128
- 85 Engelender S, Isacson O. The threshold theory for Parkinson’s disease. Trends Neurosci 2017; 40: 4-14
- 86 Laperle AH, Sances S, Yucer N. et al. iPSC modeling of young-onset Parkinson’s disease reveals a molecular signature of disease and novel therapeutic candidates. Nat Med 2020; 26: 289-299
- 87 Riederer P, Jellinger KA, Kolber P. et al. Lateralisation in Parkinson disease. Cell Tissue Res 2018; Jul;. 373 (01) : 297-312