Skip to main content
SpringerLink
Log in

Neural Transplantation in Dementia

  • Conference paper
Restoration of Brain Function by Tissue Transplantation

Part of the book series: Basic and Clinical Aspects of Neuroscience ((BASIC,volume 5))

  • 41 Accesses

Abstract

As other chapters in this volume attest, the intracerebral grafting (ICG) of neural tissue is now well established as an effective strategy for anatomic reconstruction and functional repair in a variety of neural systems in the brain. Moreover, preliminary trials have commenced of the clinical applications of the ICG paradigm to a number of neurodegenerative diseases, most notably parkinsonism (see chapter by Brundin and Lindvall, this volume). One of the fundamental conditions for the development of a rational ICG therapy is the identification of the target population(s) of cells central to the disease process, which one consequently seeks to replace. The failure as yet to identify the primary basis of the disease process in human dementia not only represents the biggest problem for developing an effective ICG strategy for the disease but restricts even the determination of the fundamental issue whether such a strategy might be feasible.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

Senile dementia:

A class of diseases of old age, leading to progressive functional deterioration of cognition, attention, learning, and memory.

Alzheimer’s disease (AD):

A neurodegenerative disease that is the commonest cause of dementia. Its diagnosis is based on the presence post mortem of specific neuropathologic hallmarks: neurofibrillary tangles and senile plaques in the neocortex and hippocampus.

Senile dementia of the Alzheimer type (SDAT):

Because a final diagnosis of Alzheimer’s disease can only be made post mortem, patients whose dementia is characteristic of AD should in life strictly be diagnosed as having SDAT.

Neurofibrillary tangles (NFTs):

Dense accumulations of fibrous deposits within the cytoplasm of neurons, usually visualized in silver-stained brain sections. In AD, they are predominant in large pyramidal neurons of the neocortex and hippocampus.

Paired helical filaments (PHFs):

Electron-microscopic studies have shown that the NFTs of AD are made up of fine filaments that are twisted together to form regular paired helical structures.

Tau protein:

The major protein constituent of the PHFs. It has recently been sequenced and is found to occur in 6 isoforms in the brain.

Senile (or neuritic) plaques:

Extracellular tangles of neurites with a core of amyloid. Plaque deposits in the cortex and hippocampus are a second diagnostic neuropathologic feature of AD.

Amyloid:

Amyloid is an extracellular deposit in many tissues that is defined by its particular optical properties when viewed under polarized light.

β/A4 amyloid protein:

The particular form of amyloid that is deposited in extracellular spaces and around blood vessels in AD:It has been sequenced and is found to consist of a 42 amino acid protein. It is thought to be an abnormal cleavage product of the precursor protein APP.

Amyloid precursor protein (APP):

Cloning of the β/A4 protein has enabled the sequencing of the full APP precursor protein. There are 3 isoforms in the brain, 695,751, and 770 amino acids long. APP is believed to be a membrane-bound protein, with the β/A4 protein located close to its C-terminal end in the region thought to span the membrane. The function of APP in the intact CNS is at present unknown.

References

  1. Bartus RT, Dean RL, Beer B, Lippa AS (1982) The cholinergic hypothesis of geriatric memory dysfunction. Science 217: 408–417

    Article  PubMed  CAS  Google Scholar 

  2. Bredesen DE, Kane DJ, Holtzman DM, Epstein CJ (1991) Reaggregating cultures of trisomy 16 brain. Soc Neurosci Abstr 17: 1064

    Google Scholar 

  3. Candy JM, Perry RH, Perry EK, Irving D, Blessed G, Fairbairn AF, Tomlinson BE (1983) Pathological changes in the nucleus of Meynert in Alzheimer’s and Parkinson’s diseases. J Neurol Sci 54: 277–289

    Article  Google Scholar 

  4. Cassel JC, Kelche C, Peterson GM, Ballough GP, Goepp I, Will B (1991) Graft-induced behavioral recovery from subcallosal septo- hippocampal damage in rats depends on maturity stage of donor tissue. Neuroscience 45: 571–586

    Article  PubMed  CAS  Google Scholar 

  5. Collier TJ, Gash DM, Sladek JR (1988) Transplantation of nor-epinephrine neurons into aged rats improves performance of a learned task. Brain Res 448: 77–87

    Article  PubMed  CAS  Google Scholar 

  6. Coyle JT, Price DL, DeLong MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219: 1184–1190

    Article  PubMed  CAS  Google Scholar 

  7. Doering LC, Aguayo AJ (1987) Hirano bodies and other cytoskeletal abnormalities in fetal rat CNS grafts isolated for long periods in peripheral nerve. Brain Res 401: 178–184

    Article  PubMed  CAS  Google Scholar 

  8. Drachman DA, Sahakian BJ (1980) Memory, aging and pharmacosystems. In: Stein D (ed) The psychobiology of aging: problems and perspectives. Elsevier/North Holland, Amsterdam, pp 347–368

    Google Scholar 

  9. Dunnett SB (1990) Neural transplantation in animal models of dementia. Eur J Neurosci 2: 567–587

    Article  PubMed  Google Scholar 

  10. Dunnett SB (1991) Cholinergic grafts, ageing and memory in rats. Trends Neurosci 14: 371–376

    Article  PubMed  CAS  Google Scholar 

  11. Dunnett SB, Barth TM (1991) Animal models of Alzheimer’s disease and dementia. In: Willner P (ed) Behavioural models in psychopharmacology. Cambridge University Press, London, pp 359–418

    Google Scholar 

  12. Dunnett SB, Low WC, Iversen SD, Stenevi U, Björklund A (1982) Septal transplants restore maze learning in rats with fornix-fimbria lesions. Brain Res 251: 335–348

    Article  PubMed  CAS  Google Scholar 

  13. Dunnett SB, Martel FL, Rogers DC, Finger S (1989) Factors affecting septal graft amelioration of differential reinforcement of low rates ( DRL) and activity deficits after fimbria-fornix lesions. Restor Neurol Neurosci 1: 83–92

    PubMed  CAS  Google Scholar 

  14. Dunnett SB, Badman F, Rogers DC, Evenden JL, Iversen SD (1989) Cholinergic grafts in the neocortex or hippocampus of aged rats: reduction of delay-dependent deficits in the delayed non- matching to position task. Exp Neurol 102: 57–64

    Article  Google Scholar 

  15. Eriksdotter-Nilsson M, Gerhardt G, Seiger A, Hoffer B, Granholm A-C (1989) Multiple changes in noradrenergic mechanisms in the coeruleo-hippocampal pathway during aging. Structural and functional correlates in intraocular double grafts. Neurobiol Aging 10: 117–124

    Article  PubMed  CAS  Google Scholar 

  16. Eriksdotter-Nilsson M, Gerhardt G, Seiger A, Olson L, Hoffer B, Granholm A-C (1989) Age-related alterations in noradrenergic in-put to the hippocampal formation: structural and functional studies in intraocular transplants. Brain Res 478: 269–280

    Article  PubMed  CAS  Google Scholar 

  17. Fischer W, Wictorin K, Björklund A, Williams LR, Varon S, Gage FH (1987) Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329: 65–68

    Article  PubMed  CAS  Google Scholar 

  18. Gage FH, Björklund A (1986) Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism. J Neurosci 6: 2837–2847

    PubMed  CAS  Google Scholar 

  19. Gage FH, Dunnett SB, Stenevi U, Björklund A (1983) Aged rats: recovery of motor impairment by intrastriatal nigral grafts. Science 221: 966–969

    Article  PubMed  CAS  Google Scholar 

  20. Gage FH, Björklund A, Stenevi U, Dunnett SB, Kelly PAT (1984) Intrahippocampal septal grafts ameliorate learning deficits in aged rats. Science 225: 533–536

    Article  PubMed  CAS  Google Scholar 

  21. Gage FH, Wolff JA, Rosenberg MB, Xu L, Yee J-K, Shults C, Friedmann T (1987) Grafting genetically modified cells to the brain: pos-sibilities for the future. Neuroscience 23: 795–807

    Article  PubMed  CAS  Google Scholar 

  22. Gage FH, Fisher LJ, Jinnah JHA, Rosenberg MB, Tuszynski M, Friedmann T (1990) Grafting genetically modified cells to the brain: conceptual and technical issues. Prog Brain Res 82: 1–10

    Article  PubMed  CAS  Google Scholar 

  23. Hefti F, Weiner WJ (1986) Nerve growth factor and Alzheimer’s disease. Ann Neurol 20: 275–281

    Article  PubMed  CAS  Google Scholar 

  24. Hodges H, Allen Y, Kershaw T, Lantos PL, Gray JA, Sinden J (1991) Effects of cholinergic-rich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system: I. Amelioration of cognitive deficits by transplants into cortex and hippocampus but not into basal forebrain. Neuroscience 45: 587–607

    Article  PubMed  CAS  Google Scholar 

  25. Hodges H, Allen Y, Kershaw T, Lantos PL, Gray JA, Sinden J (1991) Effects of cholinergicrich neural grafts on radial maze performance of rats after excitotoxic lesions of the forebrain cholinergic projection system: II. Cholinergic drugs as probes to investigate lesion-induced deficits and transplant-induced functional recovery. Neuroscience 45: 609–623

    Article  PubMed  CAS  Google Scholar 

  26. Hohmann CF, Capone G, Oster-Granite M-L, Coyle JT (1990) Transplantation of brain tissue from murine trisomy 16 into euploid hosts: effects of gene imbalance on brain development. Prog Brain Res 82: 203–214

    Article  PubMed  CAS  Google Scholar 

  27. Hohmann CF, Capone GT, Diggs AM, Coyle JT (1991) Expression of amyloid in cortical transplants of trisomy 16 mouse. Soc Neurosci Abstr 17: 51

    Google Scholar 

  28. Kang J, Lemaire HG, Unterbeck A, Salbaum M, Masters CL, Grzeschik KH, Multhaup G Beyreuther K, Muller-Hill B (1987) The precursor of Alzheimer’s disease amyloid protein resembles a cell-surface receptor. Nature 325: 733–736

    Article  PubMed  CAS  Google Scholar 

  29. Kromer LF, Björklund A, Stenevi U (1981) Regeneration of the septohippocampal pathways in adult rats is promoted by utilizing embryonic hippocampal implants as bridges. Brain Res 210: 173–200

    Article  PubMed  CAS  Google Scholar 

  30. Mann DMA (1988) Neuropathological and neurochemical aspects of Alzheimer’s disease. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 20. Plenum, New York, pp 1–67

    Chapter  Google Scholar 

  31. Messersmith DJ, Fabrazzo M, Mocchetti I, Kromer LF (1991) Effects of sciatic nerve transplants after fimbria-fornix lesion: examination of the role of nerve growth factor. Brain Res 557: 293–297

    Article  PubMed  CAS  Google Scholar 

  32. Nilsson OG, Shapiro ML, Olton DS, Gage FH, Björklund A (1987) Spatial learning and memory following fimbria-fornix transection and grafting of fetal septal neurons to the hippocampus. Exp Brain Res 67: 195–215

    Article  PubMed  CAS  Google Scholar 

  33. Nilsson OG, Brundin P, Björklund A (1990) Amelioration of spatial memory impairment by intrahippocampal grafts of mixed septal and raphe tissue in rats with combined cholinergic and serotonergic denervation of the forebrain. Brain Res 515: 193–206

    Article  PubMed  CAS  Google Scholar 

  34. Oliver C, Holland AJ (1986) Down’s syndrome and Alzheimer’s disease: a review. Psychol Med 16: 307–322

    Article  PubMed  CAS  Google Scholar 

  35. Olson L, Backlund E-O, Ebendal T, Freedman R, Hamberger B, Hansson P, Hoffer B, Lindblom U, Meyerson B, Stromberg I, Sydow O, Seiger A (1991) Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson’s disease. Arch Neurol 48: 373–381

    Article  PubMed  CAS  Google Scholar 

  36. Pearson RCA, Powell TPS (1989) The neuroanatomy of Alzheimer’s disease. Rev Neurosci 2: 101–122

    Article  PubMed  CAS  Google Scholar 

  37. Perry EK (1986) The cholinergic hypothesis - ten years on. Br Med Bull 42: 63–69

    PubMed  CAS  Google Scholar 

  38. Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J ii: 1457–1459

    Article  Google Scholar 

  39. Quon D, Wang Y, Catalano R, Marian Scardina J, Murakami K, Cordell B (1991) Formation of p-amyloid protein deposits in brains of transgenic mice. Nature 352: 239–241

    Article  PubMed  CAS  Google Scholar 

  40. Richards S-J (1991) The neuropathology of Alzheimer’s disease investigated by transplantation of mouse trisomy 16 hippocampal tissues. Trends Neurosci 14: 334–338

    Article  PubMed  CAS  Google Scholar 

  41. Richards S-J, Waters JJ, Abraham CJ, Sparkman DR, White CL, Beyreuther K, Masters CL, Dunnett SB (1991) Transplants of mouse trisomy 16 hippocampus provide an in vivo model of the neuropathology of Alzheimer’s disease. EMBO J10: 297–303

    CAS  Google Scholar 

  42. Richter-Levin G, Segal M (1989) Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies. Brain Res 478: 184–186

    Article  PubMed  CAS  Google Scholar 

  43. Ridley RM, Baker HF (1991) Can fetal neural transplants restore function in monkeys with lesion-induced behavioural deficits? Trends Neurosci 14: 366–370

    Article  PubMed  CAS  Google Scholar 

  44. Rosenberg MB, Friedmann T, Robertson RC, Tuszynski M, Wolff JA, Breakefield XO, Gage FH (1988) Grafting of genetically modified cells to the damaged brain: restorative effects of NGF expression. Science 242: 1575–1578

    Article  PubMed  CAS  Google Scholar 

  45. Sofroniew MV, Pearson RCA (1985) Degeneration of cholinergic neurons in the basal nucleus following kainic acid or TV-methyl-D- aspartic acid application to the cerebral cortex in the rat. Brain Res 339: 186–190

    Article  PubMed  CAS  Google Scholar 

  46. Sofroniew MV, Isacson O, Björklund A (1986) Cortical grafts prevent atrophy of cholinergic basal nucleus neurons induced by ex-citotoxic cortical damage. Brain Res 378: 409–415

    Article  PubMed  CAS  Google Scholar 

  47. Sofroniew MV, Dunnett SB, Isacson O (1990) Remodelling of intrinsic and afferent systems during loss and replacement of cortical neurons. Prog Brain Res 82: 313–320

    Article  PubMed  CAS  Google Scholar 

  48. Springer JE, Collier TJ, Sladek JR, Loy R (1988) Transplantation of male mouse submaxillary gland increases survival of axotomised basal forebrain neurons. J Neurosci Res 19: 291–296

    Article  PubMed  CAS  Google Scholar 

  49. Stoll J, Ault B, Rapoport SI, Fine A (1991) Examination of Alzheimer-type pathology in mouse trisomy 16 neurons maintained by transplantation. Soc Neurosci Abstr 17: 1064

    Google Scholar 

  50. Tomlinson BE, Corsellis JAN (1984) Aging and the dementias. In: Hume Adams J, Corsellis JAN, Duchen IW (eds) Greenfield’s neuropathology. Wiley, New York, pp 951–1025

    Google Scholar 

  51. Tomlinson BE, Blessed G, Roth M (1970) Observations on the brains of demented old people. J Neurol Sci 11: 205–242

    Article  PubMed  CAS  Google Scholar 

  52. Vanderwolf CH (1987) Neartotal loss of “learning” and “memory” as a result of combined cholinergic and serotonergic blockade in the rat. Behav Brain Res 23: 43–57

    Article  PubMed  CAS  Google Scholar 

  53. Wischik CM, Novak M, Thorensen HC, Edwards PC, Runswick MJ, Jakes R, Walker JE, Milstein C, Roth M, Klug A (1988) Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer’s disease. Proc Natl Acad Sci USA 85: 4506–4510

    Article  PubMed  CAS  Google Scholar 

  54. Yamaguchi F, Richards SJ, Beyreuther K, Dunnett SB (1991) Transgenic mice for the amyloid precursor protein 695 isoform show spatial memory impairment. NeuroReport 2: 781–784

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Psychology, University of Cambridge, Cambridge, UK

    S. B. Dunnett

Authors
  1. S. B. Dunnett
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Restorative Neurology Unit (RNU) Department of Neurology, University Hospital, 221 85, Lund, Sweden

    Olle Lindvall

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Dunnett, S.B. (1993). Neural Transplantation in Dementia. In: Lindvall, O. (eds) Restoration of Brain Function by Tissue Transplantation. Basic and Clinical Aspects of Neuroscience, vol 5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77718-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-77718-9_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-55823-1

  • Online ISBN: 978-3-642-77718-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation