Cerebrolysin modulates pronerve growth factor/nerve growth factor ratio and ameliorates the cholinergic deficit in a transgenic model of Alzheimer's disease

Journal of Neuroscience Research

Volumn 91, Issue 2, 2013, Pages 167-177

  Ubhi, Kiren ^a   Rockenstein, Edward ^a   Vazquez Roque, Ruben ^b   Mante, Michael ^a   Inglis, Chandra ^a   Patrick, Christina ^a   Adame, Anthony ^a   Fahnestock, Margaret ^c   Doppler, Edith ^d   Novak, Philip ^d   Moessler, Herbert ^d   Masliah, Eliezer ^a,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b INSTITUTO POLITÉCNICO NACIONAL   (Mexico)

^c MCMASTER UNIVERSITY   (Canada)

^d EVER Neuro Pharma GmbH   (Austria)

^e UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Amyloid precursor protein; Neurodegene ration; Synapses

Indexed keywords

AMYLOID PRECURSOR PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; CEREBROLYSIN; CILIARY NEUROTROPHIC FACTOR; MESSENGER RNA; NERVE GROWTH FACTOR; NEUROTROPHIC FACTOR; NEUROTROPHIN RECEPTOR; NEUROTROPHIN RECEPTOR P75; NEUROTROPIN 3; NEUROTROPIN 4; PRONERVE GROWTH FACTOR; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BASAL AMYGDALA; CONTROLLED STUDY; HIPPOCAMPUS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MOUSE; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL;

ALZHEIMER DISEASE; AMINO ACIDS; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CHOLINE O-ACETYLTRANSFERASE; CHOLINERGIC AGENTS; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; HUMANS; MICE; MICE, TRANSGENIC; MUTATION; NERVE GROWTH FACTORS; NEUROPROTECTIVE AGENTS; RECEPTOR, TRKA; RECEPTORS, NERVE GROWTH FACTOR; RNA, MESSENGER;

EID: 84870884137     PISSN: 03604012     EISSN: 10974547     Source Type: Journal    
DOI: 10.1002/jnr.23142     Document Type: Article

References (74)

1. Akai F, Hiruma S, Sato T, Iwamoto N, Fujimoto M, Ioku M, Hashimoto S. 1992. Neurotrophic factor-like effect of FPF1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. Histol Histopathol 7: 213-221.
2. Alvarez XA, Cacabelos R, Laredo M, Couceiro V, Sampedro C, Varela M, Corzo L, Fernandez-Novoa L, Vargas M, Aleixandre M, Linares C, Granizo E, Muresanu D, Moessler H. 2006. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. Eur J Neurol 13: 43-54.
3. Alvarez XA, Cacabelos R, Sampedro C, Aleixandre M, Linares C, Granizo E, Doppler E, Moessler H. 2011a. Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin. Eur J Neurol 18: 59-68.
4. Alvarez XA, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, Linares C, Granizo E, Garcia-Fantini M, Baurecht W, Doppler E, Moessler H. 2011b. Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with Cerebrolysin and donepezil. Curr Alzheimer Res 8: 583-591.
5. Blanchard J, Chohan MO, Li B, Liu F, Iqbal K, Grundke-Iqbal I. 2010a. Beneficial effect of a CNTF tetrapeptide on adult hippocampal neurogenesis, neuronal plasticity, and spatial memory in mice. J Alzheimers Dis 21: 1185-1195.
6. Blanchard J, Wanka L, Tung YC, Cardenas-Aguayo Mdel C, LaFerla FM, Iqbal K, Grundke-Iqbal I. 2010b. Pharmacologic reversal of neurogenic and neuroplastic abnormalities and cognitive impairments without affecting Abeta and tau pathologies in 3 × Tg-AD mice. Acta Neuropathol 120: 605-621.
7. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello NA, Muller FJ, Loring JF, Yamasaki TR, Poon WW, Green KN, LaFerla FM. 2009. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A 106: 13594-13599.
8. Boncristiano S, Calhoun ME, Kelly PH, Pfeifer M, Bondolfi L, Stalder M, Phinney AL, Abramowski D, Sturchler-Pierrat C, Enz A, Sommer B, Staufenbiel M, Jucker M. 2002. Cholinergic changes in the APP23 transgenic mouse model of cerebral amyloidosis. J Neurosci 22: 3234-3243.
9. Capsoni S, Cattaneo A. 2006. On the molecular basis linking nerve growth factor (NGF) to Alzheimer's disease. Cell Mol Neurobiol 26: 619-633.
10. Chen H, Tung YC, Li B, Iqbal K, Grundke-Iqbal I. 2007. Trophic factors counteract elevated FGF-2-induced inhibition of adult neurogenesis. Neurobiol Aging 28: 1148-1162.
11. Chohan MO, Li B, Blanchard J, Tung YC, Heaney AT, Rabe A, Iqbal K, Grundke-Iqbal I. 2011. Enhancement of dentate gyrus neurogenesis, dendritic and synaptic plasticity and memory by a neurotrophic peptide. Neurobiol Aging 32: 1420-1434.
12. Crews L, Adame A, Patrick C, Delaney A, Pham E, Rockenstein E, Hansen L, Masliah E. 2010. Increased BMP6 levels in the brains of Alzheimer's disease patients and APP transgenic mice are accompanied by impaired neurogenesis. J Neurosci 30: 12252-12262.
13. Crews L, Patrick C, Adame A, Rockenstein E, Masliah E. 2011. Modulation of aberrant CDK5 signaling rescues impaired neurogenesis in models of Alzheimer's disease. Cell Death Dis 2: e120.
14. Cuello AC, Bruno MA. 2007. The failure in NGF maturation and its increased degradation as the probable cause for the vulnerability of cholinergic neurons in Alzheimer's disease. Neurochem Res 32: 1041-1045.
15. Cuello AC, Bruno MA, Allard S, Leon W, Iulita MF. 2010. Cholinergic involvement in Alzheimer's disease. A link with NGF maturation and degradation. J Mol Neurosci 40: 230-235.
16. DeKosky ST, Scheff SW, Styren SD. 1996. Structural correlates of cognition in dementia: quantification and assessment of synapse change. Neurodegeneration 5: 417-421.
17. 308/Y transgenic model of Rett syndrome. Acta Neuropathol 116: 425-437.
18. EBEWENeuroPharma GmbH. 2009. Cerebrolysin solution for injection: summary of product characteristics. Unterach, Austria: EVER Neuro Pharma GmbH.
19. Fahnestock M, Michalski B, Xu B, Coughlin MD. 2001. The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer's disease. Mol Cell Neurosci 18: 210-220.
20. Francis-Turner L, Valouskova V. 1996. Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short-term study. Neurosci Lett 202: 193-196.
21. Francis-Turner L, Valouskova V, Mokry J. 1996. The long-term effect of NGF, b-FGF and Cerebrolysin on the spatial memory after fimbria-fornix lesion in rats. J Neural Transm 47( Suppl): 277.
22. Fugere M, Day R. 2005. Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition. Trends Pharmacol Sci 26: 294-301.
23. Gaitetdinova DD, Semenov VV, Ismagilov MF, Kharitonov VS. 2006. [Clastogenic, aneugenic, pro- and antioxidant properties of some neurotropic preparations]. Eksp Klin Farmakol 69: 58-62.
24. Harrington AW, Leiner B, Blechschmitt C, Arevalo JC, Lee R, Morl K, Meyer M, Hempstead BL, Yoon SO, Giehl KM. 2004. Secreted proNGF is a pathophysiological death-inducing ligand after adult CNS injury. Proc Natl Acad Sci U S A 101: 6226-6230.
25. Havas D, Hutter-Paier B, Ubhi K, Rockenstein E, Crailsheim K, Masliah E, Windisch M. 2011. A longitudinal study of behavioral deficits in an AbetaPP transgenic mouse model of Alzheimer's disease. J Alzheimers Dis 25: 231-243.
26. Kar S, Slowikowski SP, Westaway D, Mount HT. 2004. Interactions between beta-amyloid and central cholinergic neurons: implications for Alzheimer's disease. J Psychiatry Neurosci 29: 427-441.
27. Kichev A, Ilieva EV, Pinol-Ripoll G, Podlesniy P, Ferrer I, Portero-Otin M, Pamplona R, Espinet C. 2009. Cell death and learning impairment in mice caused by in vitro modified pro-NGF can be related to its increased oxidative modifications in Alzheimer disease. Am J Pathol 175: 2574-2585.
28. Li B, Wanka L, Blanchard J, Liu F, Chohan MO, Iqbal K, Grundke-Iqbal I. 2010. Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. FEBS Lett 584: 3359-3365.
29. Lim KC, Tyler CM, Lim ST, Giuliano R, Federoff HJ. 2007. Proteolytic processing of proNGF is necessary for mature NGF regulated secretion from neurons. Biochem Biophys Res Commun 361: 599-604.
30. Longo FM, Yang T, Knowles JK, Xie Y, Moore LA, Massa SM. 2007. Small molecule neurotrophin receptor ligands: novel strategies for targeting Alzheimer's disease mechanisms. Curr Alzheimer Res 4: 503-506.
31. Marksteiner J, Pirchl M, Ullrich C, Oberbauer H, Blasko I, Lederer W, Hinterhuber H, Humpel C. 2008. Analysis of cerebrospinal fluid of Alzheimer patients. Biomarkers and toxic properties. Pharmacology 82: 214-220.
32. Masliah E. 1995. Mechanisms of synaptic dysfunction in Alzheimer's disease. Histol Histopathol 10: 509-519.
33. Masliah E, Rockenstein E. 2000. Genetically altered transgenic models of Alzheimer's disease. J Neural Transm 59( Suppl): 175-183.
34. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DWJr, Morris JC. 2001. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology 56: 127-129.
35. Masliah E, Alford M, Adame A, Rockenstein E, Galasko D, Salmon D, Hansen LA, Thal LJ. 2003. Abeta1-42 promotes cholinergic sprouting in patients with AD and Lewy body variant of AD. Neurology 61: 206-211.
36. Masliah E, Crews L, Hansen L. 2006. Synaptic remodeling during aging and in Alzheimer's disease. J Alzheimers Dis 9( Suppl 3): 91-99.
37. Nagahara AH, Merrill DA, Coppola G, Tsukada S, Schroeder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JM, Rockenstein E, Chao MV, Koo EH, Geschwind D, Masliah E, Chiba AA, Tuszynski MH. 2009. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease. Nat Med 15: 331-337.
38. Onishchenko LS, Gaikova ON, Yanishevskii SN. 2008. Changes at the focus of experimental ischemic stroke treated with neuroprotective agents. Neurosci Behav Physiol 38: 49-54.
39. Paxinos G, Franklin K. 2001. The mouse brain in stereotaxic coordinates. San Diego: Academic Press.
40. NTR. Am J Pathol 166: 533-543.
41. Peng S, Wuu J, Mufson EJ, Fahnestock M. 2004. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol 63: 641-649.
42. Peng S, Wuu J, Mufson EJ, Fahnestock M. 2005. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. J Neurochem 93: 1412-1421.
43. Plosker GL, Gauthier S. 2009. Cerebrolysin: a review of its use in dementia. Drugs Aging 26: 893-915.
44. Plosker GL, Gauthier S. 2010. Spotlight on cerebrolysin in dementia. CNS Drugs 24: 263-266.
45. NTR and apoptosis. Am J Pathol 169: 119-131.
46. Ren J, Sietsma D, Qiu S, Moessler H, Finklestein SP. 2007. Cerebrolysin enhances functional recovery following focal cerebral infarction in rats. Restor Neurol Neurosci 25: 25-31.
47. Rockenstein EM, McConlogue L, Tan H, Power M, Masliah E, Mucke L. 1995. Levels and alternative splicing of amyloid beta protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem 270: 28257-28267.
48. 1-42. J Neurosci Res 66: 573-582.
49. Rockenstein E, Mallory M, Mante M, Alford M, Windisch M, Moessler H, Masliah E. 2002. Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease. J Neural Transm 61( Suppl): 327-336.
50. Rockenstein E, Adame A, Mante M, Moessler H, Windisch M, Masliah E. 2003. The neuroprotective effects of Cerebrolysin in a transgenic model of Alzheimer's disease are associated with improved behavioral performance. J Neural Transm 110: 1313-1327.
51. Rockenstein E, Adame A, Mante M, Larrea G, Crews L, Windisch M, Moessler H, Masliah E. 2005. Amelioration of the cerebrovascular amyloidosis in a transgenic model of Alzheimer's disease with the neurotrophic compound cerebrolysin. J Neural Transm 112: 269-282.
52. Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, Crews L, Moessler H, Masliah E. 2006. Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer's disease. J Neurosci Res 83: 1252-1261.
53. Rockenstein E, Crews L, Masliah E. 2007a. Transgenic animal models of neurodegenerative diseases and their application to treatment development. Adv Drug Deliv Rev 59: 1093-1102.
54. Rockenstein E, Mante M, Adame A, Crews L, Moessler H, Masliah E. 2007b. Effects of Cerebrolysin on neurogenesis in an APP transgenic model of Alzheimer's disease. Acta Neuropathol 113: 265-275.
55. Rockenstein E, Ubhi K, Doppler E, Novak P, Moessler H, Li B, Blanchard J, Grundke-Iqbal I, Iqbal K, Mante M, Adame A, Crews L, Masliah E. 2011a. Regional comparison of the neurogenic effects of CNTF-derived peptides and Cerebrolysin in AbetaPP transgenic mice. J Alzheimers Dis (in press).
56. Rockenstein E, Ubhi K, Pham E, Michael S, Doppler E, Novak P, Inglis C, Mante M, Adame A, Alvarez XA, Moessler H, Masliah E. 2011b. Beneficial effects of a neurotrophic peptidergic mixture persist for a prolonged period following treatment interruption in a transgenic model of Alzheimer's disease. J Neurosci Res 89: 1812-1821.
57. Ruther E, Ritter R, Apecechea M, Freytag S, Windisch M. 1994. Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry 27: 32-40.
58. Ruther E, Ritter R, Apecechea M, Freytag S, Gmeinbauer R, Windisch M. 2000. Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy. J Neural Transm 107: 815-829.
59. Scheff S, DeKosky S, Price D. 1990. Quantitative assessment of cortical synaptic density in Alzheimer's disease. Neurobiol Aging 11: 29-37.
60. Schindowski K, Belarbi K, Buee L. 2008. Neurotrophic factors in Alzheimer's disease: role of axonal transport. Genes Brain Behav 7( Suppl 1): 43-56.
61. Scott SA, Mufson EJ, Weingartner JA, Skau KA, Crutcher KA. 1995. Nerve growth factor in Alzheimer's disease: increased levels throughout the brain coupled with declines in nucleus basalis. J Neurosci 15: 6213-6221.
62. Seidah NG, Chretien M. 1999. Proprotein and prohormone convertases: a family of subtilases generating diverse bioactive polypeptides. Brain Res 848: 45-62.
63. Serkina EV, Gromova OA, Torshin I, Sotnikova N, Nikonov AA. 2008. [Cerebrolysin alleviates perinatal CNS disorders through the autoimmune modulation and antioxidant protection]. Zh Nevrol Psikhiatr Im S S Korsakova 108: 62-66.
64. Spencer B, Marr RA, Rockenstein E, Crews L, Adame A, Potkar R, Patrick C, Gage FH, Verma IM, Masliah E. 2008. Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice. BMC Neurosci 9: 109.
65. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, Ledermann B, Burki K, Frey P, Paganetti PA, Waridel C, Calhoun ME, Jucker M, Probst A, Staufenbiel M, Sommer B. 1997. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci U S A 94: 13287-13292.
66. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. 1991. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30: 572-580.
67. Tomidokoro Y, Harigaya Y, Matsubara E, Ikeda M, Kawarabayashi T, Okamoto K, Shoji M. 2000. Impaired neurotransmitter systems by Abeta amyloidosis in APPsw transgenic mice overexpressing amyloid beta protein precursor. Neurosci Lett 292: 155-158.
68. Trojanowski JQ, Shin RW, Schmidt ML, Lee VM. 1995. Relationship between plaques, tangles, and dystrophic processes in Alzheimer's disease. Neurobiol Aging 16: 335-340; discussion 341-335.
69. Tuszynski MH. 2007. Nerve growth factor gene therapy in Alzheimer disease. Alzheimer Dis Assoc Disord 21: 179-189.
70. Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G, Potkin SG, Fallon J, Hansen L, Mufson EJ, Kordower JH, Gall C, Conner J. 2005. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11: 551-555.
71. Veinbergs I, Mante M, Mallory M, Masliah E. 2000. Neurotrophic effects of Cerebrolysin in animal models of excitotoxicity. J Neural Transm 59( Suppl): 273-280.
72. Wong TP, Debeir T, Duff K, Cuello AC. 1999. Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes. J Neurosci 19: 2706-2716.
73. Wronski R, Kronawetter S, Hutter-Paier B, Crailsheim K, Windisch M. 2000. A brain derived peptide preparation reduces the translation dependent loss of a cytoskeletal protein in primary cultured chicken neurons. J Neural Transm 59( Suppl): 263-272.
74. Zhang C, Chopp M, Cui Y, Wang L, Zhang R, Zhang L, Lu M, Szalad A, Doppler E, Hitzl M, Zhang ZG. 2010. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke. J Neurosci Res 88: 3275-3281.