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American Journal of Alzheimer's Disease and Other Dementias logoLink to American Journal of Alzheimer's Disease and Other Dementias
. 2004 May-Jun;19(3):153–160. doi: 10.1177/153331750401900303

Ganstigmine and donepezil improve neurodegeneration in AD11 antinerve growth factor transgenic mice

Simona Capsoni 1, Sabina Giannotta 2, Marco Stebel 3, Addys Ancheta Garcia, Roberta de Rosa 4, Gino Villetti, Bruno Pietro Imbimbo, Claudio Pietra 5, Antonino Cattaneo 6
PMCID: PMC10833932  PMID: 15214201

Abstract

Ganstigmine (CHF2819) is an acetylcholinesterase inhibitor that increases acetylcholine in rat hippocampus and ameliorates scopolamine-induced amnesia. In this article, we examined whether and how ganstigmine might prevent or rescue the neurodegenerative phenotype in AD11 antinerve growth factor (anti-NGF) mice, a transgenic model for Alzheimer's disease. The effects of ganstigmine were compared with those obtained after administration of donepezil. Results demonstrate that intraperitoneal and oral administration of ganstigmine and donepezil can reverse the cholinergic and behavioral deficit in AD11 mice but not the amyloid and phosphotau accumulation, uncovering different mechanisms leading to neurodegeneration in AD11 mice.

Keywords: Alzheimer's disease, ganstigmine, donepezil, therapeutic agents, acetylcholinesterase inhibitors

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Contributor Information

Simona Capsoni, Lay Line Genomics S.p.A., Rome, Italy..

Sabina Giannotta, International School for Advanced Studies, Trieste, Italy..

Marco Stebel, Lay Line Genomics S.p.A., Rome, and C.S.P.A., University of Trieste, Trieste, Italy..

Roberta de Rosa, Lay Line Genomics S.p.A., Rome, Italy..

Claudio Pietra, R & D Department, Chiesi Farmaceutici S.p.A., Parma, Italy..

Antonino Cattaneo, Lay Line Genomics S.p.A., Rome, and the International School for Advanced Studies, Trieste, Italy..

References

  1. Selkoe DJ: Alzheimer's disease: Genes, proteins, and therapy. Physiol Rev. 2001; 81(2): 741-766. [DOI] [PubMed] [Google Scholar]
  2. Giacobini E: Cholinergic function and Alzheimer's disease. Int J Geriatr Psychiatry.2003; 18(Suppl 1): S1-S5. [DOI] [PubMed] [Google Scholar]
  3. Tariot PN, Federoff HJ: Current treatment for Alzheimer disease and future prospects. Alzheimer Dis Assoc Disord.2003; 17(Suppl 4): S105-S113. [DOI] [PubMed] [Google Scholar]
  4. Pietra C, Villetti G, Bolzoni PT, et al.: Cholinesterase inhibitory activity of new geneserine derivatives. Alzheimer Dis Assoc Disord. 1999: 689-696. [Google Scholar]
  5. Trabace L, Cassano T, Steardo L, et al.: Biochemical and neurobehavioral profile of CHF2819, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease. J Pharmacol Exp Ther.2000; 294(1): 187-194. [PubMed] [Google Scholar]
  6. Windisch M, Hutter-Paier B, Jerkovic L, et al.: The protective effect of ganstigmine against amyloid beta 25-35 neurotoxicity on chicken cortical neurons is independent from the cholinesterase inhibition. Neurosci Lett.2003; 341(3): 181-184. [DOI] [PubMed] [Google Scholar]
  7. Capsoni S, Giannotta S, Cattaneo A: Beta-amyloid plaques in a model for sporadic Alzheimer's disease based on transgenic anti-nerve growth factor antibodies. Mol Cell Neurosci.2002; 21(1): 15-28. [DOI] [PubMed] [Google Scholar]
  8. Capsoni S, Giannotta S, Cattaneo A: Early events of alzheimer like neurodegeneration in anti-nerve growth factor transgenic mice. Brain Aging.2002; 2: 24-43. [Google Scholar]
  9. Capsoni S, Ugolini G, Comparini A, et al.: Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice. Proc Natl Acad Sci.2000; 97(12): 6826-6831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ruberti F, Capsoni S, Comparini A, et al.: Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen, and skeletal muscle dystrophy. J Neurosci.2000; 20(7): 2589-2601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pesavento E, Capsoni S, Domenici L, et al.: Acute cholinergic rescue of synaptic plasticity in the neurodegenerating cortex of antinerve-growth-factor mice. Eur J Neurosci.2002; 15(6): 1030-1036. [DOI] [PubMed] [Google Scholar]
  12. Franklin KBJ, Paxinos GT: The Mouse Brain in Stereotaxic Coordinates.San Diego: Academic Press, 1997. [Google Scholar]
  13. Russo C, Salis S, Dolcini V, et al.: Amino-terminal modification and tyrosine phosphorylation of [corrected] carboxy-terminal fragments of the amyloid precursor protein in Alzheimer's disease and Down's syndrome brain. Neurobiol Dis. 2001; 8(1): 173-180. [DOI] [PubMed] [Google Scholar]
  14. Capsoni S, Giannotta S, Cattaneo A: Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice. Proc Natl Acad Sci. 2002; 99(19): 12432-12437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ridley RM, Baker, HF: A critical evaluation of monkey models of amnesia and dementia. Brain Res Rev.1991; 16: 15-37. [DOI] [PubMed] [Google Scholar]
  16. Beatty W, Winn P, Adams R, et al.: Preserved cognitive skills in dementia of the Alzheimer type. Arch Neurol.1994; 51: 1040-1046. [DOI] [PubMed] [Google Scholar]
  17. Ennaceur A, Delacour J: A new one-trial test for neurobiological studies of memory in rats: 1: Behavioral data. J Behav Brain Res. 1988; 31: 47-59. [DOI] [PubMed] [Google Scholar]
  18. Giacobini E: Cholinesterase inhibitors stabilize Alzheimer disease. Neurochem Res. 2000; 25 (9-10): 1185-1190. [DOI] [PubMed] [Google Scholar]

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