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Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease

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Abstract

The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum — globulus pallidus — thalamus — striatum. Striatal neurone degeneration is a hallmark in Huntington’s disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-μm-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington’s disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri’s principle and the optical disector. Mean neurone number in the controls was 646,952 ± 129,668 cells versus 291,763 ± 60, 122 in Huntington’s disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 ± 3,028,944 versus 6,961,989 ± 2,241,543 in Huntington’s disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas’ impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington’s disease patients = 24.4 ±8.1; controls = 15.0 ± 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington’s disease.

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References

  1. Albin RL, Young AB (1988) Somatosensory phenomena in Huntington’s disease. Mov Disord 3:343–346

    Article  PubMed  CAS  Google Scholar 

  2. Arikuni T, Kubota K (1986) The organization of prefrontocaudate projections and their laminar origin in the macaque monkey: a retrograde study using HRP-gel. J Comp Neurol 244: 492–510

    Article  PubMed  CAS  Google Scholar 

  3. Avanzini G, Girotti F, Caraceni T, Spreafico R (1979) Oculomotor disorders in Huntington’s chorea. J Neurol Neurosurg Psychiatry 42:581–589

    Article  PubMed  CAS  Google Scholar 

  4. Bollen E, Reulen JP, Heyer JC den, Kamp W van der, Roos RA, Buruma OJ (1986) Horizontal and vertical saccadic eye movement abnormalities in Huntington’s chorea. J Neurol Sci 74:11–22

    Article  PubMed  CAS  Google Scholar 

  5. Bortz J, Lienert GA, Boenke K (1990) Verteilungsfreie Methoden in der Biostatistik. Springer, Berlin Heidelberg New York

    Google Scholar 

  6. Brodal A (1981) Neurological anatomy in relation to clinical medicine. Oxford Universtiy Press, New York

    Google Scholar 

  7. Byers RK, Gilles FH, Fung C (1973) Huntington’s disease in children. Neuropathologic study of four cases. Neurology 23: 561–569

    PubMed  CAS  Google Scholar 

  8. Campbell AMG, Corner B, Norman RM, Urich H (1961) The rigid form of Huntington’s disease. J Neurol Neurosurg Psychiatry 24:71–77

    Article  PubMed  CAS  Google Scholar 

  9. Chudler EH, Dong WK (1995) The role of the basal ganglia in nociception and pain. Pain 60:3–38

    Article  PubMed  CAS  Google Scholar 

  10. Craig AD, Bushnell MC, Zhang ET, Blomqvist A (1994) A thalamic nucleus specific for pain and temperature sensation. Nature 372:770–773

    Article  PubMed  CAS  Google Scholar 

  11. De la Monte SM, Vonsattel JP, Richardson EP Jr (1988) Morphometric demonstration of atrophic changes in the cerebral cortex, white matter, and neostriatum in Huntington’s disease. J Neuropathol Exp Neurol 47:516–525

    Article  PubMed  Google Scholar 

  12. Dom R, Malfroid M, Baro F (1976) Neuropathology of Huntington’s chorea. Studies of the ventrobasal complex of the thalamus. Neurology 26:64–68

    PubMed  CAS  Google Scholar 

  13. Druga R, Rokyta R, Benes V (1991) Thalamocaudate projections in the macaque monkey: a horseradish peroxidase study. J Hirnforsch 32:765–774

    PubMed  CAS  Google Scholar 

  14. Dunlap CB (1927) Pathologic changes in Huntington’s chorea: with special reference to the corpus striatum. Arch Neurol Psychiatry 18:867–943

    Google Scholar 

  15. Fenelon G, François C, Percheron G, Yelnik J (1991) Topographic distribution of the neurons of the central complex (centre median-parafascicular complex) and of other thalamic neurons projecting to the striatum in macaques. Neuroscience 45: 495–510

    Article  PubMed  CAS  Google Scholar 

  16. Fénelon G, Yelnik J, François C, Percheron G (1994) Central complex of the primate thalamus: a quantitative analysis of neuronal morphology. J Comp Neurol 342:463–479

    Article  PubMed  Google Scholar 

  17. François C, Percheron G, Parent A, Sadikot AF, Fénelon G, Yelnik J (1991) Topography of the projection from the central complex of the thalamus to the sensorimotor striatal territory in monkeys. J Comp Neurol 305:17–34

    Article  PubMed  Google Scholar 

  18. Gailyas F (1981) An argyrophil III method for the demonstration of fibrous neuroglia. Acta Morphol Acad Sci Hung 29: 185–193

    Google Scholar 

  19. Goldman-Rakic PS, Selemon LD (1986) Topography of corticostriatal projections in nonhuman primates and implications for functional parcellation of the neostriatum. In: Jones EG, Peters A (eds) Cerebral cortex, vol 5. Sensory-motor areas and aspects of cortical connectivity. Plenum Press, New York, pp 447–466

    Google Scholar 

  20. Gundersen HJ (1986) Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones; in memory of William R. Thompson. J Microsc 143: 3–45

    PubMed  CAS  Google Scholar 

  21. Gundersen HJ, Jensen EB (1987) The efficiency of systematic sampling in stereology and its prediction. J Microsc 147: 229–263

    PubMed  CAS  Google Scholar 

  22. Gundersen HJ, Bendtsen TF, Korbo L, et al (1988) Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS 96:379–394

    PubMed  CAS  Google Scholar 

  23. Heinsen H, Heinsen YL (1991) Serial thick, frozen, gallocyanin-stained sections of human central nervous system. J Histotechnol 14:167–173

    Google Scholar 

  24. Heinsen H, Henn R, Eisenmenger W, Götz M, Bohl J, Bethke B, Lockemann U, Püschel K (1994) Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes. Anat Embryol 190:181–194

    Article  PubMed  CAS  Google Scholar 

  25. Heinsen H, Strik M, Bauer M, Luther K, Ulmar G, Gangnus D, Jungkunz G, Eisenmenger W, Götz M (1994) Cortical and striatal neurone number in Huntington’s disease. Acta Neuropathol 88:320–333

    Article  PubMed  CAS  Google Scholar 

  26. Hopf A (1966) Volumetrische Untersuchungen zur vergleichenden Anatomie des Thalamus. J Hirnforsch 8:25–38

    Google Scholar 

  27. Huerta MF, Krubitzer LA, Kaas JH (1986) Frontal eye fields defined by intracortical microstimulation in squirrel monkeys, owl monkeys, and macaque monkeys. I. Subcortical connections. J Comp Neurol 253:415–439

    Article  PubMed  CAS  Google Scholar 

  28. Jervis GA (1963) Huntington’s chorea in childhood. Arch Neurol 9:244–257

    PubMed  CAS  Google Scholar 

  29. Jones EG (1984) Laminar distribution of cortical efferent cells. In: Peters A, Jones EG (eds) Cerebral cortex, vol 1. Cellular components of the cerebral cortex. Plenum Press, New York, pp 521–553

    Google Scholar 

  30. Kötter R, Meyer N (1992) The limbic system: a review of its empirical foundation. Behav Brain Res 52:105–127

    Article  PubMed  Google Scholar 

  31. Künzle H, Akert K (1977) Efferent connections of cortical area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. J Comp Neurol 173: 147–164

    Article  PubMed  Google Scholar 

  32. Lange HW (1981) Quantitative changes of telencephalon, diencephalon, and mesencephalon in Huntington’s chorea, postencephalitic, and idiopathic parkinsonism. Verh Anat Ges 75: 923–925

    Google Scholar 

  33. Lange HW, Aulich A (1986) Die Hirnatrophie bei Huntingtonscher Krankheit. Neuroanatomische und neuroradiologische Untersuchungen. In: Oepen H (ed) Die Huntingtonsche Krankheit. Zur Symptomatik, Ätiologie, Früherkennung, Therapie und Selbsthilfe, Hippokrates, Stuttgart, pp 25–41

    Google Scholar 

  34. Lange HW, Thorner G, Hopf A, Schröder KF (1976) Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci 28:401–425

    Article  PubMed  CAS  Google Scholar 

  35. Lasker AG, Zee DS, Hain TC, Folstein SE, Singer HS (1988) Saccades in Huntington’s disease: slowing and dysmetria. Neurology 38: 427–431

    PubMed  CAS  Google Scholar 

  36. Leigh RJ, Newman SA, Folstein SE, Lasker AG, Jensen BA (1983) Abnormal ocular motor control in Huntington’s disease. Neurology 33:1268–1275

    PubMed  CAS  Google Scholar 

  37. Lesch A, Bogerts B (1984) The diencephalon in schizophrenia: evidence for reduced thickness of the periventricular grey matter. Eur Arch Psychiatr Neurol Sci 234:212–219

    Article  CAS  Google Scholar 

  38. Martin JJ (1966) Topographie et signification des lésions thalamique dans la maladie de Creutzfeldt-Jakob et les formes apparentées. J Hirnforsch 8: 137–159

    PubMed  CAS  Google Scholar 

  39. Martin JJ (1967) Sur une dégénérescence systematisée du centre median. J Hirnforsch 9:346–357

    Google Scholar 

  40. McCaughey WTE (1961) The pathologic spectrum of Huntington’s chorea. J Nerv Ment Dis 133:91–103

    Article  Google Scholar 

  41. Mehler WR (1980) Subcortical afferent connections of the amygdala in the monkey. J Comp Neurol 190:733–762

    Article  PubMed  CAS  Google Scholar 

  42. Nakano K, Hasegawa Y, Tokushige A, Nakagawa S, Kayahara T, Mizuno N (1990) Topographical projections from the thalamus, subthalamic nucleus and pedunculopontine tegmental nucleus to the striatum of the Japanese monkey, Macaca fuscata. Brain Res 537:54–68

    Article  PubMed  CAS  Google Scholar 

  43. Nakano T, Iwabuchi K, Yagishita S, Amano N, Akagi M, Yamamoto Y (1985) An autopsy case of dentatorubropallidoluysian atrophy (DRPLA) clinically diagnosed as Huntington’s chorea. No To Shinkei 37:767–774

    PubMed  CAS  Google Scholar 

  44. Oepen G, Clarenbach P, Thoden U (1981) Disturbance of eye movements in Huntington’s chorea. Arch Psychiatr Nervenkr 229:205–213

    Article  PubMed  CAS  Google Scholar 

  45. Oepen G, Mohr U, Willmes K, Thoden U (1985) Huntington’s disease: visuomotor disturbance in patients and offspring. J Neurol Neurosurg Psychiatry 48:426–433

    Article  PubMed  CAS  Google Scholar 

  46. Ohje C (1990) Thalamus. In: Paxinos G (ed) The human nervous system. Academic Press, San Diego, pp 439–468

    Google Scholar 

  47. Parent A (1990) Extrinsic connections of the basal ganglia. Trends Neurosci 13:254–258

    Article  PubMed  CAS  Google Scholar 

  48. Parent A, De Bellefeuille L (1983) The pallidointralaminar and pallidonigral projections in primate as studied by retrograde double-labeling method. Brain Res 278: 11–27

    Article  PubMed  CAS  Google Scholar 

  49. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. 1. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev 20:91–127

    Article  PubMed  CAS  Google Scholar 

  50. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. 2. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Rev 20:128–154

    Article  PubMed  CAS  Google Scholar 

  51. Parent A, Mackey A, De Bellefeuille L (1983) The subcortical afferents to caudate nucleus and putamen in primate: a fluorescence retrograde double labeling study. Neuroscience 10: 1137–1150

    Article  PubMed  CAS  Google Scholar 

  52. Romeis B (1948) Mikroskopische Technik. Oldenburg, München

    Google Scholar 

  53. Royce GJ (1987) Recent research on the centromedian and parafascicular nuclei. In: Carpenter MB, Jayaraman A (eds) The basal ganglia II. Plenum Press, New York, pp 293–319

    Google Scholar 

  54. Russchen FT, Amaral DG, Price JL (1985) The afferent connections of the substantia innominata in the monkey, Macaca fascicularis. J Comp Neurol 242:1–27

    Article  PubMed  CAS  Google Scholar 

  55. Sadikot AF, Parent A, François C (1992) The centre median and parafascicular thalamic nuclei project respectively to the sensorimotor and associative-limbic striatal territories in the squirrel monkey. Brain Res 510:161–165

    Article  Google Scholar 

  56. Sadikot AF, Parent A, François C (1992) Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a PHA-L study of sbucortical projections. J Comp Neurol 315: 137–159

    Article  PubMed  CAS  Google Scholar 

  57. Schröder KF, Hopf A, Lange H, Thörner G (1975) Morphometrisch-statistische Strukturanalysen des Striatum, Pallidum und Nucleus subthalamicus beim Menschen. I. Striatum. J Hirnforsch 16:333–350

    PubMed  Google Scholar 

  58. Simma K (1950) Das Centrum medianum bei Chorea Huntington. Monatsschr Psychiatr Neurol 119:99–119

    Article  Google Scholar 

  59. Smith Y, Parent A (1986) Differential connections of caudate nucleus and putamen in the squirrel monkey (Saimiri sciweus). Neuroscience 18:347–371

    Article  PubMed  CAS  Google Scholar 

  60. Smith Y, Bennett BD, Bolam JP, Parent A, Sadikot AF (1994) Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey. J Comp Neurol 344:1–19

    Article  PubMed  CAS  Google Scholar 

  61. Stanton GB, Goldberg ME, Bruce CJ (1988) Frontal eye field efferents in the macaque monkey. I. Subcortical pathways and topography of striatal and thalamic terminal fields. J Comp Neurol 271:473–492

    Article  PubMed  CAS  Google Scholar 

  62. Starr A (1967) A disorder of rapid eye movements in Huntington’s chorea. Brain 90:545–564

    Article  PubMed  CAS  Google Scholar 

  63. Vogt C, Vogt O (1920) Zur Lehre der Erkrankungen des striaren Systems. J Psychol Neurol 25 [Suppl 3]: 631–846

    Google Scholar 

  64. Vogt C, Vogt O (1942) Morphologische Gestaltungen unter normalen und pathogenen Bedingungen. Ein hirnanatomischer Beitrag zu ihrer Kenntnis. J Psychol Neurol 50:161–524

    Google Scholar 

  65. Walker AE (1982) Normal and pathological physiology of the thalamus. In: Schaltenbrand G, Walker AE (eds) Stereotaxy of the human brain. Anatomical, physiological and clinical applications. Thieme, Stuttgart New York, pp 181–217

    Google Scholar 

  66. West MJ, Gundersen HJG (1990) Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296: 1–22

    Article  PubMed  CAS  Google Scholar 

  67. West MJ, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497

    Article  PubMed  CAS  Google Scholar 

  68. Xuereb JH, Perry RH, Candy JM, Perry EK, Marshall E, Bonham JR (1991) Nerve cell loss in the thalamus in Alzheimer’s disease and Parkinson’s disease. Brain 114:1363–1380

    PubMed  Google Scholar 

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Heinsen, H., Rüb, U., Gangnus, D. et al. Nerve cell loss in the thalamic centromedian-parafascicular complex in patients with Huntington’s disease. Acta Neuropathol 91, 161–168 (1996). https://doi.org/10.1007/s004010050408

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