IGF2 ameliorates amyloidosis, increases cholinergic marker expression and raises BMP9 and neurotrophin levels in the hippocampus of the APPswePS1dE9 Alzheimer's disease model mice

PLoS ONE

Volumn 9, Issue 4, 2014, Pages

  Mellott, Tiffany J ^a   Pender, Sarah M ^a   Burke, Rebecca M ^a   Langley, Erika A ^a   Blusztajn, Jan Krzysztof ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCHOLINE; ACETYLCHOLINE SYNTHESIZING ENZYME; ACTIVIN RECEPTOR LIKE KINASE 1; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; BONE MORPHOGENETIC PROTEIN 9; BRAIN DERIVED NEUROTROPHIC FACTOR; CHOLINE ACETYLTRANSFERASE; DOUBLECORTIN; NERVE GROWTH FACTOR; NEUROTROPHIN; NEUROTROPHIN 3; SOMATOMEDIN B; SOMATOMEDIN C; UNCLASSIFIED DRUG; ACTIVIN RECEPTOR 1; ACVRL1 PROTEIN, MOUSE; AMYLOID BETA PROTEIN; BIOLOGICAL MARKER; DOUBLECORTIN PROTEIN; GLIAL FIBRILLARY ACIDIC PROTEIN; MICROTUBULE ASSOCIATED PROTEIN; NEUROPEPTIDE;

ALZHEIMER DISEASE; AMYLOID PLAQUE; AMYLOIDOSIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN LEVEL; CELL SIZE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; FEMALE; GENE EXPRESSION; GLIOSIS; HIPPOCAMPUS; MALE; MOUSE; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PROTEIN EXPRESSION; TRANSGENIC MOUSE; WILD TYPE; ANIMAL; CHOLINERGIC NERVE CELL; COMPLICATION; DISEASE MODEL; ENZYMOLOGY; HUMAN; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY;

ACTIVIN RECEPTORS, TYPE I; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOIDOSIS; ANIMALS; BIOMARKERS; CHOLINE O-ACETYLTRANSFERASE; CHOLINERGIC NEURONS; DISEASE MODELS, ANIMAL; GLIAL FIBRILLARY ACIDIC PROTEIN; GLIOSIS; GROWTH DIFFERENTIATION FACTOR 2; HIPPOCAMPUS; HUMANS; INSULIN-LIKE GROWTH FACTOR II; MICE; MICE, TRANSGENIC; MICROTUBULE-ASSOCIATED PROTEINS; NERVE GROWTH FACTORS; NEUROGENESIS; NEUROPEPTIDES; PLAQUE, AMYLOID;

EID: 84899621158     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0094287     Document Type: Article

References (96)

1. Benilova I, Karran E, De Strooper B (2012) The toxic Ab oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci 15: 349-357.
2. Bowen DM, Smith CB, White P, Davison AN (1976) Neurotransmitter related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 99: 459-496.
3. Mufson EJ, Counts SE, Perez SE, Ginsberg SD (2008) Cholinergic system during the progression of Alzheimer's disease: therapeutic implications. Expert Rev Neurother 8: 1703-1718.
4. Grothe M, Heinsen H, Teipel SJ (2012) Atrophy of the cholinergic Basal forebrain over the adult age range and in early stages of Alzheimer's disease. Biol Psychiatry 71: 805-813.
5. Pedersen WA, Kloczewiak MA, Blusztajn JK (1996) Amyloid b-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain. Proc Natl Acad Sci USA 93: 8068-8071. (Pubitemid 26277166)
6. Kar S, Seto D, Gaudreau P, Quirion R (1996) b-Amyloid-related peptides inhibit potassium-evoked acetylcholine release from hippocampal slices. J Neurosci 16: 1034-1040. (Pubitemid 26140859)
7. Kar S, Issa AM, Seto D, Auld DS, Collier B, et al. (1998) Amyloid b-peptide inhibits high-affinity choline uptake and acetylcholine release in rat hippocampal slices. J Neurochem 70: 2179-2187. (Pubitemid 28207844)
8. Nunes-Tavares N, Santos LE, Stutz B, Brito-Moreira J, Klein WL, et al. (2012) Inhibition of choline acetyltransferase as a mechanism for cholinergic dysfunction induced by amyloid-beta oligomers. J Biol Chem.
9. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, et al. (2005) Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis 8: 247-268.
10. Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, et al. (2011) A critical role for IGF-II in memory consolidation and enhancement. Nature 469: 491-497.
11. Alberini CM and Chen DY (2012) Memory enhancement: consolidation, reconsolidation and insulin-like growth factor 2. Trends Neurosci 35: 274-283.
12. Agis-Balboa RC, Arcos-Diaz D, Wittnam J, Govindarajan N, Blom K, et al. (2011) A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories. Embo J 30: 4071-4083.
13. Ouchi Y, Banno Y, Shimizu Y, Ando S, Hasegawa H, et al. (2013) Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11.2 deletion-associated schizophrenia can be rescued by IGF2. J Neurosci 33: 9408-9419.
14. Lupien SB, Bluhm EJ, Ishii DN (2003) Systemic insulin-like growth factor-I administration prevents cognitive impairment in diabetic rats, and brain IGF regulates learning/memory in normal adult rats. J Neurosci Res 74: 512-523. (Pubitemid 37352073)
15. Bracko O, Singer T, Aigner S, Knobloch M, Winner B, et al. (2012) Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis. J Neurosci 32: 3376-3387.
16. Kar S, Seto D, Doré S, Hanisch UK, Quirion R (1997) Insulin-like growth factors-I and-II differentially regulate endogenous acetylcholine release from the rat hippocampal formation. Proc Natl Acad Sci USA 94: 14054-14059. (Pubitemid 28009708)
17. Hawkes C, Jhamandas JH, Harris KH, Fu W, MacDonald RG, et al. (2006) Single transmembrane domain insulin-like growth factor-II/mannose-6-phosphate receptor regulates central cholinergic function by activating a G-proteinsensitive, protein kinase C-dependent pathway. J Neurosci 26: 585-596. (Pubitemid 43237124)
18. Napoli I, Blusztajn JK, Mellott TJ (2008) Prenatal choline supplementation in rats increases the expression of IGF2 and its receptor IGF2R and enhances IGF2-induced acetylcholine release in hippocampus and frontal cortex. Brain Res 1237: 124-135.
19. Jarvis K, Assis-Nascimento P, Mudd LM, Montague JR (2007) Beta-amyloid toxicity and reversal in embryonic rat septal neurons. Neurosci Lett 423: 184-188. (Pubitemid 47285476)
20. Stein TD, Anders NJ, DeCarli C, Chan SL, Mattson MP, et al. (2004) Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci 24: 7707-7717. (Pubitemid 39186826)
21. Jankowsky JL, Slunt HH, Ratovitski T, Jenkins NA, Copeland NG, et al. (2001) Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol Eng 17: 157-165. (Pubitemid 32409891)
22. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, et al. (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet 13: 159-170. (Pubitemid 38111354)
23. Tallini YN, Shui B, Greene KS, Deng KY, Doran R, et al. (2006) BAC transgenic mice express enhanced green fluorescent protein in central and peripheral cholinergic neurons. Physiol Genomics 27: 391-397. (Pubitemid 46708790)
24. Schnitzler AC, Mellott TJ, Lopez-Coviella I, Tallini YN, Kotlikoff MI, et al. (2010) BMP9 (bone morphogenetic protein 9) induces NGF as an autocrine/paracrine cholinergic trophic factor in developing basal forebrain neurons. J Neurosci 30: 8221-8228.
25. Gö tz J, Ittner LM (2008) Animal models of Alzheimer's disease and frontotemporal dementia. Nat Rev Neurosci 9: 532-544. (Pubitemid 351873467)
26. Perez SE, Dar S, Ikonomovic MD, Dekosky ST, Mufson EJ (2007) Cholinergic forebrain degeneration in the APPswe/PS1DeltaE9 transgenic mouse. Neurobiol Dis 28: 3-15. (Pubitemid 47429971)
27. Machova E, Rudajev V, Smyckova H, Koivisto H, Tanila H, et al. (2010) Functional cholinergic damage develops with amyloid accumulation in young adult APPswe/PS1dE9 transgenic mice. Neurobiol Dis 38: 27-35.
28. Payette DJ, Xie J, Guo Q (2007) Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1 M146V mutant knock-in mice. Brain Res 1135: 12-21. (Pubitemid 46176822)
29. Goto Y, Niidome T, Hongo H, Akaike A, Kihara T, et al. (2008) Impaired muscarinic regulation of excitatory synaptic transmission in the APPswe/PS1dE9 mouse model of Alzheimer's disease. Eur J Pharmacol 583: 84-91.
30. Nikolajsen GN, Jensen MS, West MJ (2011) Cholinergic axon length reduced by 300 meters in the brain of an Alzheimer mouse model. Neurobiol Aging 32: 1927-1931.
31. Savonenko A, Xu GM, Melnikova T, Morton JL, Gonzales V, et al. (2005) Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis 18: 602-617. (Pubitemid 40332718)
32. Park JH, Widi GA, Gimbel DA, Harel NY, Lee DH, et al. (2006) Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice. J Neurosci 26: 13279-13286. (Pubitemid 46011638)
33. O'Leary TP, Brown RE (2009) Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav Brain Res 201: 120-127.
34. Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Lauren J, et al. (2010) Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci 30: 6367-6374.
35. Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, et al. (2010) Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology 35: 870-880.
36. Kemppainen S, Rantamaki T, Jeronimo-Santos A, Lavasseur G, Autio H, et al. (2011) Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice. Neurobiol Aging 33: 1122.e1123-1139.
37. Garcia-Alloza M, Robbins EM, Zhang-Nunes SX, Purcell SM, Betensky RA, et al. (2006) Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol Dis 24: 516-524. (Pubitemid 44716680)
38. Glenn MJ, Kirby ED, Gibson EM, Wong-Goodrich SJ, Mellott TJ, et al. (2008) Age-related declines in exploratory behavior and markers of hippocampal plasticity are attenuated by prenatal choline supplementation in rats. Brain Res 1237: 110-123.
39. Wong-Goodrich SJ, Mellott TJ, Glenn MJ, Blusztajn JK, Williams CL (2008) Prenatal choline supplementation attenuates neuropathological response to status epilepticus in the adult rat hippocampus. Neurobiol Dis 30: 255-269.
40. Glenn MJ, Gibson EM, Kirby ED, Mellott TJ, Blusztajn JK, et al. (2007) Prenatal choline availability modulates hippocampal neurogenesis and neurogenic responses to enriching experiences in adult female rats. Eur J Neurosci 25: 2473-2482. (Pubitemid 46625934)
41. Lopez-Coviella I, Mellott TJ, Schnitzler AC, Blusztajn JK (2011) BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype. PLoS ONE 6: e21166.
42. Lopez-Coviella I, Berse B, Krauss R, Thies RS, Blusztajn JK (2000) Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 289: 313-316. (Pubitemid 30469912)
43. Lopez-Coviella I, Follettie MT, Mellott TJ, Kovacheva VP, Slack BE, et al. (2005) Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons. Proc Natl Acad Sci U S A 102: 6984-6989. (Pubitemid 40675428)
44. Bissonnette CJ, Lyass L, Bhattacharyya BJ, Belmadani A, Miller RJ, et al. (2011) The controlled generation of functional basal forebrain cholinergic neurons from human embryonic stem cells. Stem Cells 29: 802-811.
45. Brown MA, Zhao Q, Baker KA, Naik C, Chen C, et al. (2005) Crystal structure of BMP-9 and functional interactions with pro-region and receptors. J Biol Chem 280: 25111-25118. (Pubitemid 40934603)
46. Scharpfenecker M, van Dinther M, Liu Z, van Bezooijen RL, Zhao Q, et al. (2007) BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 120: 964-972. (Pubitemid 46638511)
47. David L, Mallet C, Mazerbourg S, Feige JJ, Bailly S (2007) Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 109: 1953-1961. (Pubitemid 46348192)
48. Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, et al. (2012) Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem 287: 27313-27325.
49. Couillard-Despres S, Winner B, Karl C, Lindemann G, Schmid P, et al. (2006) Targeted transgene expression in neuronal precursors: watching young neurons in the old brain. Eur J Neurosci 24: 1535-1545. (Pubitemid 44427522)
50. Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, et al. (2005) Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci 21: 1-14. (Pubitemid 40193870)
51. Kamphuis W, Orre M, Kooijman L, Dahmen M, Hol EM (2012) Differential cell proliferation in the cortex of the APPswePS1dE9 Alzheimer's disease mouse model. Glia 60: 615-629.
52. Kamphuis W, Mamber C, Moeton M, Kooijman L, Sluijs JA, et al. (2012) GFAP isoforms in adult mouse brain with a focus on neurogenic astrocytes and reactive astrogliosis in mouse models of Alzheimer disease. PLoS ONE 7: e42823.
53. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, et al. (2008) Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 451: 720-724. (Pubitemid 351220570)
54. Mandrekar-Colucci S, Karlo JC, Landreth GE (2012) Mechanisms underlying the rapid peroxisome proliferator-activated receptor-gamma-mediated amyloid clearance and reversal of cognitive deficits in a murine model of Alzheimer's disease. J Neurosci 32: 10117-10128.
55. Knusel B, Michel PP, Schwaber JS, Hefti F (1990) Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. J Neurosci 10: 558-570. (Pubitemid 20089077)
56. Knusel B, Hefti F (1991) Trophic actions of IGF-I, IGF-II and insulin on cholinergic and dopaminergic brain neurons. Adv Exp Med Biol 293: 351-360.
57. Konishi Y, Takahashi K, Chui D-H, Rosenfeld RG, Himeno M, et al. (1994) Insulin-like growth factor II promotes in vitro cholinergic development of mouse septal neurons: Comparison with the effects of insulin-like growth factor I. Brain Res 649: 53-61. (Pubitemid 24197196)
58. Gage SL, Keim SR, Low WC (1990) Effects of insulin-like growth factor II (IGFII) on transplanted cholinergic neurons from the fetal septal nucleus. Prog Brain Res 82: 73-80. (Pubitemid 20299603)
59. Nitsch RM, Slack BE, Wurtman RJ, Growdon JH (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258: 304-307.
60. Ramos-Rodriguez JJ, Pacheco-Herrero M, Thyssen D, Murillo-Carretero MI, Berrocoso E, et al. (2013) Rapid beta-Amyloid Deposition and Cognitive Impairment After Cholinergic Denervation in APP/PS1 Mice. J Neuropathol Exp Neurol 72: 272-285.
61. Laursen B, Mork A, Plath N, Kristiansen U, Bastlund JF (2013) Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. Behav Brain Res 240: 146-152.
62. Medeiros R, Kitazawa M, Caccamo A, Baglietto-Vargas D, Estrada-Hernandez T, et al. (2011) Loss of muscarinic M1 receptor exacerbates Alzheimer's diseaselike pathology and cognitive decline. Am J Pathol 179: 980-991.
63. Wyss-Coray T, Lin C, Yan FR, Yu GQ, Rohde M, et al. (2001) TGF-b1 promotes microglial amyloid-b clearance and reduces plaque burden in transgenic mice. NatMed 7: 612-618. (Pubitemid 32448330)
64. Lemere CA, Spooner ET, LaFrancois J, Malester B, Mori C, et al. (2003) Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice. Neurobiol Dis 14: 10-18. (Pubitemid 37103175)
65. Maier M, Seabrook TJ, Lazo ND, Jiang L, Das P, et al. (2006) Short amyloidbeta (Abeta) immunogens reduce cerebral Abeta load and learning deficits in an Alzheimer's disease mouse model in the absence of an Abeta-specific cellular immune response. J Neurosci 26: 4717-4728. (Pubitemid 44315311)
66. Burke RM, Norman TA, Haydar TF, Slack BE, Leeman SE, et al. (in press) BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A.
67. Crews L, Adame A, Patrick C, Delaney A, Pham E, et al. (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.
68. Li D, Tang J, Xu H, Fan X, Bai Y, et al. (2008) Decreased hippocampal cell proliferation correlates with increased expression of BMP4 in the APPswe/PS1DeltaE9 mouse model of Alzheimer's disease. Hippocampus 18: 692-698. (Pubitemid 352032394)
69. Tang J, Song M, Wang Y, Fan X, Xu H, et al. (2009) Noggin and BMP4 comodulate adult hippocampal neurogenesis in the APP(swe)/PS1(DeltaE9) transgenic mouse model of Alzheimer's disease. Biochem Biophys Res Commun 385: 341-345.
70. Schliebs R, Arendt T (2011) The cholinergic system in aging and neuronal degeneration. Behav Brain Res 221: 555-563.
71. Tuszynski MH, Thal L, Pay M, Salmon DP, U HS, et al. (2005) A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11: 551-555. (Pubitemid 40691288)
72. Alderson RF, Alterman AL, Barde Y-A, Lindsay RM (1990) Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron 5: 297-306. (Pubitemid 20294980)
73. Nonomura T, Hatanaka H (1992) Neurotrophic effect of brain-derived neurotrophic factor on basal forebrain cholinergic neurons in culture from postnatal rats. Neurosci Res 14: 226-233. (Pubitemid 23000723)
74. Nonner D, Barrett EF, Barrett JN (2000) Brief exposure to neurotrophins produces a calcium-dependent increase in choline acetyltransferase activity in cultured rat septal neurons. J Neurochem 74: 988-999. (Pubitemid 30104294)
75. Nonner D, Panickar K, Barrett EF, Barrett JN (2004) Bone morphogenetic proteins and neurotrophins provide complementary protection of septal cholinergic function during phosphatase inhibitor-induced stress. J Neurochem 91: 77-87. (Pubitemid 39314939)
76. Burgess A, Aubert I (2006) Polysialic acid limits choline acetyltransferase activity induced by brain-derived neurotrophic factor. J Neurochem 99: 797-806. (Pubitemid 44583439)
77. Ward NL, Hagg T (2000) BDNF is needed for postnatal maturation of basal forebrain and neostriatum cholinergic neurons in vivo. Exp Neurol 162: 297-310. (Pubitemid 30217725)
78. Knusel B, Beck KD, Winslow JW, Rosenthal A, Burton LE, et al. (1992) Brainderived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci 12: 4391-4402.
79. Morse JK, Wiegand SJ, Anderson K, You Y, Cai N, et al. (1993) Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection. J Neurosci 13: 4146-4156. (Pubitemid 23299940)
80. Robertson RT, Baratta J, Yu J, Guthrie KM (2006) A role for neurotrophin-3 in targeting developing cholinergic axon projections to cerebral cortex. Neuroscience 143: 523-539. (Pubitemid 44724938)
81. Lesne S, Gabriel C, Nelson DA, White E, Mackenzie ET, et al. (2005) Aktdependent expression of NAIP-1 protects neurons against amyloid-b toxicity. J Biol Chem 280: 24941-24947. (Pubitemid 40934586)
82. Mufson EJ, Counts SE, Ginsberg SD (2002) Gene expression profiles of cholinergic nucleus basalis neurons in Alzheimer's disease. Neurochem Res 27: 1035-1048. (Pubitemid 35316101)
83. Ginsberg SD, Che S, Wuu J, Counts SE, Mufson EJ (2006) Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease. J Neurochem 97: 475-487.
84. Devi L, Ohno M (2012) 7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease. Neuropsychopharmacology 37: 434-444.
85. Nagahara AH, Mateling M, Kovacs I, Wang L, Eggert S, et al. (2013) Early BDNF Treatment Ameliorates Cell Loss in the Entorhinal Cortex of APP Transgenic Mice. J Neurosci 33: 15596-15602.
86. Duron E, Funalot B, Brunel N, Coste J, Quinquis L, et al. (2012) Insulin-like growth factor-I and insulin-like growth factor binding protein-3 in Alzheimer's disease. J Clin Endocrinol Metab 97: 4673-4681.
87. Poirier R, Fernandez AM, Torres-Aleman I, Metzger F (2012) Early brain amyloidosis in APP/PS1 mice with serum insulin-like growth factor-I deficiency. Neurosci Lett 509: 101-104.
88. Carro E, Trejo JL, Gomez-Isla T, LeRoith D, Torres-Aleman I (2002) Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med 8: 1390-1397. (Pubitemid 36019424)
89. Doré S, Kar S, Quirion R (1997) Insulin-like growth factor I protects and rescues hippocampal neurons against b-amyloid-and human amylin-induced toxicity. Proc Natl Acad Sci USA 94: 4772-4777. (Pubitemid 27194319)
90. Kiyota T, Ingraham KL, Jacobsen MT, Xiong H, Ikezu T (2011) FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders. Proc Natl Acad Sci U S A 108: E1339-1348.
91. Niidome T, Taniuchi N, Akaike A, Kihara T, Sugimoto H (2008) Differential regulation of neurogenesis in two neurogenic regions of APPswe/PS1dE9 transgenic mice. Neuroreport 19: 1361-1364.
92. Taniuchi N, Niidome T, Goto Y, Akaike A, Kihara T, et al. (2007) Decreased proliferation of hippocampal progenitor cells in APPswe/PS1dE9 transgenic mice. Neuroreport 18: 1801-1805. (Pubitemid 350303755)
93. Hu YS, Xu P, Pigino G, Brady ST, Larson J, et al. (2010) Complex environment experience rescues impaired neurogenesis, enhances synaptic plasticity, and attenuates neuropathology in familial Alzheimer's disease-linked APPswe/PS1DeltaE9 mice. Faseb J 24: 1667-1681.
94. Demars M, Hu YS, Gadadhar A, Lazarov O (2010) Impaired neurogenesis is an early event in the etiology of familial Alzheimer's disease in transgenic mice. J Neurosci Res 88: 2103-2117.
95. Fernandez AM, Torres-Aleman I (2012) The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci 13: 225-239.
96. Hawkes C, Amritraj A, Macdonald RG, Jhamandas JH, Kar S (2007) Heterotrimeric G proteins and the single-transmembrane domain IGF-II/M6P receptor: functional interaction and relevance to cell signaling. Mol Neurobiol 35: 329-345. (Pubitemid 350129695)