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. 2006 Apr 5;12(3):300–307. doi: 10.1111/j.1750-3639.2002.tb00444.x

Reduction of Neuronal Intranuclear Rodlets Immunoreactive for Tubulin and Glucocorticoid Receptor in Alzheimer's Disease

John M Woulfe 1,✉, Robert Hammond 2,3,4, Bryan Richardson 5, Danushan Sooriabalan 3, William Parks 1, Peter Rippstein 1, David G Munoz 3,4,6
PMCID: PMC8095929  PMID: 12146798

Abstract

Neuronal intranuclear rodlets were described in normal brain over a century ago, but their functional significance and pathological relevance is unknown. Here, we show co‐localization of tubulin and glucocorticoid receptor‐like immunoreactivity in these intranuclear inclusions in human brain. In addition, we provide evidence for a massive reduction in their areal density in Alzheimer's disease brain, but not in another common neu rodegenerative condition, dementia with Lewy bodies. The marked reduction of these inclusions in Alzheimer's disease may support the concept of a role for stress hormones in Alzheimer's pathogenesis.

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References

  • 1. Akner G, Sundqvist K‐G, Denis M, Wikstrom A‐C, Gustafsson JA (1990) Immunocytochemical localization of glucocorticoid receptor in human gingival fibroblasts and evidence for a colocalization of glucocorticoid receptor with cytoplasmic microtubules. Eur J Cell Biol 53: 390–401. [PubMed] [Google Scholar]
  • 2. Behl C (1998) Effects of glucocorticoids on oxidative stress‐induced hippocampal cell death: implications for the pathogenesis of Alzheimer's disease. Exp Gerontol 33: 689–696. [DOI] [PubMed] [Google Scholar]
  • 3. Braak H, Braak E (1995) Staging of Alzheimer's disease‐related neurofibrillary changes. Neurobiol Aging 16:271–278. [DOI] [PubMed] [Google Scholar]
  • 4. Bye N, Nichols NR (1998) Adrenalectomy‐induced apoptosis and glial responsiveness during aging. Neuroreport 20: 1179–1184. [DOI] [PubMed] [Google Scholar]
  • 5. Cajal RYS (1911) Histologie du systeme nerveux de l'homme et des vertebres. II, Maloine: Paris . [Google Scholar]
  • 6. Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuro-science 61:203–209. [DOI] [PubMed] [Google Scholar]
  • 7. Conrad CD, Galea LA, Kuroda Y, McEwen BS (1996) Chronic stress impairs rat spatial memory on the Y maze and this effect is blocked by tianeptine pretreatment. Behav Neurosci 110: 1321–1334. [DOI] [PubMed] [Google Scholar]
  • 8. Davis KL, Davis BM, Greenwald BS, Mohs RC, Mathe AA, Johns CA, Horvath, TB (1986) Cortisol and Alzheimer's disease Ibasal studies. Am J Psychiatr 143:300–305. [DOI] [PubMed] [Google Scholar]
  • 9. Feldman ML, Peters A (1972) Intranuclear rods and sheets in rat cochlear nucleus. J Neurocytol 1:109–127. [DOI] [PubMed] [Google Scholar]
  • 10. Harrison PJ, Barton AJ, Najlerahim A, McDonald B, Pearson RC (1991) Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease. Psychol Med 21:855–866. [DOI] [PubMed] [Google Scholar]
  • 11. Hartmann A, Velhuis JD, Deuschle M, Standhardt H, Heuser I (1997) Twenty‐four hour cortisol release profiles in patients with Alzheimer's and Parkinson's disease: ultradian secretory pulsatility and clinical variation. Neurobiol Aging 18:285–289. [DOI] [PubMed] [Google Scholar]
  • 12. Hof PR, Cox K, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex. J Comp Neurol 301:44–54. [DOI] [PubMed] [Google Scholar]
  • 13. Husseman JW, Hallows JL, Bregman DB, Leverenz JB, Nochlin D, Jin L‐W, Vincent I (2001) Hyperphosphorylation of RNA polymerase II and reduced neuronal RNA levels precede neurofibrillary tangles in Alzheimer disease. J Neuropathol Exp Neurol 60: 1219–1232. [DOI] [PubMed] [Google Scholar]
  • 14. Kim S, Masurovsky E, Benitez H, Murray M (1970) His‐tochemical studies of the intranuclear rodlet in neurons of the chicken sympathetic and sensory ganglia. Histo-chemie 24:33–40. [DOI] [PubMed] [Google Scholar]
  • 15. Lafarga M, Berciano MT, Andres MA (1993) Protein‐syn‐thesis inhibition induces perichromatin granule accumulation and intranuclear rodlet formation in osmotically stimulated supraoptic neurons. Anat Embryol 187:363–369. [DOI] [PubMed] [Google Scholar]
  • 16. Lupien SJ, McEwen BS (1997) The acute effects of corticosteroids on cognition: integration of animal and human model studies. Brain Res Rev 24: 1–27. [DOI] [PubMed] [Google Scholar]
  • 17. Mann DM, Yates PO, Barton CM (1977) Cytomorphometric mapping of neuronal changes in senile dementia. J Neurol Neurosurg Psychiatry 40:299–302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Mann G (1894) Histological changes induced in sympathetic, motor, and sensory nerve cells by functional activity. Anat Physiol 29: 100–108. [PMC free article] [PubMed] [Google Scholar]
  • 19. Masurovsky EB, Benitez HH, Kim S‐U, Murray MR (1970) Origin, development, and nature of intranuclear rodlets and associated bodies in chicken sympathetic neurons. J Cell Biol 44: 172–191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Masliah E, LiCastro F (2000) Neuronal and synaptic loss, reactive gliosis, microglial response, and induction of complement cascade in Alzheimer's disease In: Neurodegenerative Dementias, Clark CM, Trojanowski JQ (eds.), Chapter 9, pp. 131–146, McGraw‐Hill: New York . [Google Scholar]
  • 21. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479–486. [DOI] [PubMed] [Google Scholar]
  • 22. Nasman B, Olsson T, Fagerlund M, Eriksson S, Viitanen M, Carlstrom K (1996) Blunted adrenocorticotropin and increased adrenal steroid response to human corti‐cotropin‐releasing hormone in Alzheimer's disease. Biol Psychiatry 39:311–318. [DOI] [PubMed] [Google Scholar]
  • 23. Oitzl MS, De Kloet ER (1992) Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav Neurosci 106:62–71. [DOI] [PubMed] [Google Scholar]
  • 24. Perry RH, Candy JM, Perry EK, Irving D, Blessed G, Fair‐bairn AF, Tomlinson B.E. (1982) Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus basalis of Meynert in Alzheimer's disease. Neurosci Lett 33:311–315. [DOI] [PubMed] [Google Scholar]
  • 25. Peskind ER, Wilkinson CW, Petrie EC, Schellenber GD, Raskind MA (2001) Increased csf cortisol in AD is a function of ApoE genotype. Neurology 56: 1094–1098. [DOI] [PubMed] [Google Scholar]
  • 26. Scherrer LC, Pratt WB (1992) Association of transformed glucocorticoid receptor with a cytoskeletal protein complex. J Steroid Biochem Molec Biol 41: 719–721. [DOI] [PubMed] [Google Scholar]
  • 27. Seite R, Mei N, Villet‐Luciani J (1973) Effect of electrical stimulation on nuclear microfilaments and microtubules of sympathetic neurons submitted to cycloheximide. Brain Res 50:419–423. [DOI] [PubMed] [Google Scholar]
  • 28. Seite R, Vuillet‐Luciani J, Zerbib R, Cataldo C, Escaig J, Pebusque MJ, Autillo‐Touati A (1979) Thee‐dimensional organization of tubular and filamentous nuclear inclusions and associated structures in sympathetic neurons as revealed by serial sections and tilting experiments. J Ultrastruct Res 69:211–231. [DOI] [PubMed] [Google Scholar]
  • 29. Siegesmund K, Dutta C, Fox C (1964) The ultrastructure of the intranuclear rodlet in certain nerve cells. J Anat 98:93–97. [PMC free article] [PubMed] [Google Scholar]
  • 30. Terry RD, Peck A, De Teresa R, Schechter R, Horoupian HD (1981) Some morphometric aspects of the brain in senile dementia of the Alzheimer's type. Ann Neurol 10: 184–192. [DOI] [PubMed] [Google Scholar]
  • 31. Weiner MF, Vobach S, Olsson K, Svetlik D, Risser RC (1997) Cortisol secretion and Alzheimer's disease progression. Biol Psychiatry 42: 1030–1038. [DOI] [PubMed] [Google Scholar]
  • 32. Woolley CS, Gould E, McEwen BS (1990) Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225–231. [DOI] [PubMed] [Google Scholar]
  • 33. Woulfe J, Munoz D (2000) Tubulin immunoreactive neuronal intranuclear inclusions in the human brain. Neuropathol Appl Neurobiol 26:161–171. [DOI] [PubMed] [Google Scholar]

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