Neurobiology of Aging
Volume 30, Issue 10 , Pages 1614-1625, October 2009

Septal grafts restore cognitive abilities and amyloid precursor protein metabolism

  • Eugenio Aztiria

      Affiliations

    • B.R.A.I.N. Centre for Neuroscience, Department of Physiology and Pathology, University of Trieste, Via Fleming 22, 34127 Trieste, Italy
    • These authors contributed equally to the study.
    • ,
  • Tiziana Cataudella

      Affiliations

    • B.R.A.I.N. Centre for Neuroscience, Department of Physiology and Pathology, University of Trieste, Via Fleming 22, 34127 Trieste, Italy
    • These authors contributed equally to the study.
    • ,
  • Santi Spampinato

      Affiliations

    • Department of Pharmacology, University of Bologna, Italy
    • ,
  • Giampiero Leanza

      Affiliations

    • B.R.A.I.N. Centre for Neuroscience, Department of Physiology and Pathology, University of Trieste, Via Fleming 22, 34127 Trieste, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 040 5587904; fax: +39 040 567862.

Received 1 October 2007; received in revised form 12 December 2007; accepted 19 December 2007. published online 13 February 2008.

Abstract 

Cortical cholinergic loss and amyloidogenic processing of the β-amyloid precursor protein (APP), may functionally interact in Alzheimer's disease. However, it is still unknown whether biological restoration of regulatory cholinergic inputs affects APP metabolism in vivo.

Rats immunolesioned with 192 IgG-saporin exhibited severe acquisition deficits in place navigation that were paralleled by a dramatic loss of terminal cholinergic innervation and by marked changes in the regional expression of APP-like immunoreactivity. Moreover, in these animals, we observed a drastic reduction of soluble APP (sAPP) and a concomitant increase of the unsoluble, membrane-bound fraction (mAPP).

Notably, at about 6 months post-surgery, lesioned animals implanted with reinnervating cholinergic-rich septal tissue grafts exhibited fairly normal spatial navigation abilities, as well as cortical and hippocampal APP levels that were restored up to normal or near-normal values. APP levels correlated significantly with lesion- or graft-induced changes in cholinergic innervation density, and both these measures correlated with performance in the spatial navigation task.

Thus, integrity of ascending cholinergic inputs may be required to prevent amyloidogenic processing of APP in vivo and to modulate cognitive performance.

Abbreviations: Aβ, beta amyloid peptide, AChE, acetylcholinesterase, AD, Alzheimer's disease, APP, amyloid precursor protein, sAPP, soluble APP product, mAPP, membrane-bound APP product, HBBS, Hank's balanced salt solution, P75NTR, low affinity nerve growth factor receptor, NBM, nucleus basalis magnocellularis, TBS, Tris-buffered saline, vDBB, vertical limb of the diagonal band of Broca

Keywords: Alzheimer's disease, Amyloid precursor protein, Acetylcholine, Immunotoxin, Transplantation, Spatial learning, Rat

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PII: S0197-4580(07)00491-5

doi:10.1016/j.neurobiolaging.2007.12.018

Neurobiology of Aging
Volume 30, Issue 10 , Pages 1614-1625, October 2009

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