The mTOR inhibitor rapamycin mitigates perforant pathway neurodegeneration and synapse loss in a mouse model of early-stage Alzheimer-type tauopathy

PLoS ONE

Volumn 10, Issue 11, 2015, Pages

  Siman, Robert ^a   Cocca, Ryan ^a   Dong, Yina ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MESSENGER RNA; MICROTUBULE ASSOCIATED PROTEIN; MICROTUBULE ASSOCIATED PROTEIN LIGHT CHAIN 3; PARVOVIRUS VECTOR; RAPAMYCIN; TAU PROTEIN; UNCLASSIFIED DRUG; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOSIS; CHRONIC DRUG ADMINISTRATION; CONTROLLED STUDY; DENTATE GYRUS; ENTORHINAL CORTEX; GLIOSIS; MACROGLIA; MALE; MICROGLIA; MOUSE; MOUSE MODEL; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PERFORANT NERVE TRACT; PROTEIN PHOSPHORYLATION; SYNAPSE; TAUOPATHY; ALZHEIMER DISEASE; ANIMAL; ANTAGONISTS AND INHIBITORS; AXON; DISEASE MODEL; DRUG EFFECTS; HIPPOCAMPUS; HUMAN; LONG TERM MEMORY; METABOLISM; NERVE CELL; NEURODEGENERATIVE DISEASES; PHOSPHORYLATION; TAUOPATHIES;

ALZHEIMER DISEASE; ANIMALS; AXONS; DENTATE GYRUS; DISEASE MODELS, ANIMAL; ENTORHINAL CORTEX; HIPPOCAMPUS; HUMANS; MALE; MEMORY, LONG-TERM; MICE; MICROGLIA; NEURODEGENERATIVE DISEASES; NEURONS; PERFORANT PATHWAY; PHOSPHORYLATION; SIROLIMUS; SYNAPSES; TAU PROTEINS; TAUOPATHIES; TOR SERINE-THREONINE KINASES;

EID: 84951320233     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0142340     Document Type: Article

References (59)

1. Amaral D, Lavenex P. Hippocampal anatomy, in: Andersen P, Morris R, Amaral D, Bliss T, O'Keefe J. (Eds.), The Hippocampus Book. Oxford University Press, Oxford, UK, 2007. pp. 37-114.
2. Squire LR, Wixted JT, Clark RE. Recognition memory and the medial temporal lobe: a new perspective. Nat Rev Neurosci 2007; 8: 872-883. doi: 10.1038/nrn2154 PMID: 17948032
3. Schultz H, Sommer T, Peters J. Direct evidence for domain-sensitive functional subregions in human entorhinal cortex. J Neurosci 2012; 32: 16-23. doi: 10.1523/jneurosci.5126-11.2012
4. Staubli U, Ivy G, Lynch G. Hippocampal denervation causes rapid forgetting of olfactory information in rats. Proc. Natl. Acad. Sci. USA 1984; 81: 5885-5887. PMID: 6592592
5. Kirkby DL, Higgins GA. Characterization of perforant path lesions in rodent models of memory and attention. Eur J Neurosci 1998; 10: 823-838. doi: 10.1046/j.1460-9568.1998.00087.x PMID: 9753151
6. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991; 82: 239-259. PMID: 1759558
7. Hyman BT, Van Hoesen GW, Kromer LJ, Damasio AR. Perforant pathway changes and the memory impairment of Alzheimer's disease. Ann. Neurol. 1986; 20, 472-481. PMID: 3789663
8. Gomez-Isla T, Price JL, McKeel DW Jr., Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci 1996; 16: 4491-4500. PMID: 8699259
9. Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer's disease. Arch Neurol 2001; 58: 1395-1402. PMID: 11559310
10. Kordower JH, Chu Y, Stebbins GT. DeKosky ST, Cochran EJ, Bennett D, Mufson EJ. Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment. Ann Neurol 2001; 49: 202-213. PMID: 11220740
11. Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and very mild cognitive impairment. Neurobiol Aging 2006; 27: 13773-13784.
12. Hyman BT, Van Hoesen GW, Damasio AR, Barnes CL. 1 Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science 1984; 225: 1168-1170. PMID: 6474172
13. Robinson JL, Molina-Porcel L, Corrada MM, Raible K, Lee EB, Lee VM, et al. Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest old. Brain 2014; 137: 2578-2587. doi: 10.1093/brain/awu190 PMID: 25012223
14. Pearson RC, Esiri MM, Hiorns RW, Wilcock GK, Powell TP. Anatomical correlates of the distribution of pathological changes in the neocortex in Alzheimer's disease. Proc Natl Acad Sci USA 1985; 82: 4531-4534. PMID: 3859874
15. Liu L, Droulet V, Wu JW, Witter MP, Small SA, Clelland C, Duff K. Trans-synaptic spread of tau pathology in vivo. PloS One 2012; 7: e31302. doi: 10.1371/journal.pone.0031302 PMID: 22312444
16. de Calignon A, Polydoro M, Suarez-Calvet M, William C, Adamowicz DH, Kopeikina KJ, et al. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron 2012; 73: 685-697. doi: 10.1016/j.neuron.2011.11.033 PMID: 22365544
17. Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 2013; 501: 45-51. doi: 10.1038/nature12481 PMID: 24005412
18. Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics 2008; 5: 443-457. doi: 10.1016/j.nurt.2008.05.006 1
19. Lee VM, Brunden KR, Hutton M, Trojanowski JQ. Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets. Cold Spring Harb Perspect Med 2011; 1, a006437. doi: 10.1101/cshperspect.a006437 PMID: 22229117
20. Ashe KH, Zahs KR, Probing the biology of Alzheimer's disease in mice. Neuron 2010; 66: 631-645. doi: 10.1016/j.neuron.2010.04.031 PMID: 20547123
21. Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat. Genet. 2000; 25: 402-405. PMID: 10932182
22. Wittmann CW, Wszolek MF, Shulman JM, Salvaterra PM, Lewis J, Hutton M, Feany MB. Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 2001; 293: 711-714. PMID: 11408621
23. Tanemura K, Murayama M, Akagi T, Hashikawa T, Tominaga T, Ichikawa M, et al. Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J Neurosci 2002; 22: 133-141. PMID: 11756496
24. Fath T, Eidenmuller J, Brandt R. Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer's disease. J Neurosci 2002; 22: 9733-9741. PMID: 12427828
25. Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski JQ, Schellenberg GD. Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. Proc. Natl. Acad. Sci. USA 2003; 100: 9980-9985. PMID: 12872001
26. Ramsden M, Kotilinek L, Forster C, Paulson J, McGowan E, SantaCruz K, et al. Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy. J Neurosci 2005; 25: 10637-10643. doi: 10.1523/jneurosci.3279-05.2005 PMID: 16291936
27. Congdon E, Wu JW, Myeku N. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy 2012; 8: 609-622. doi: 10.4161/auto.19048 PMID: 22361619
28. Ozcelik S, Fraser G, Castets P, Schaeffer V, Skachokova Z, Breu K, et al. Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PloS One 2013; 8: e62459. doi: 10.1371/journal.pone.0062459 PMID: 23667480
29. Caccamo A, DePinto V, Messina A, Branca C, Oddo S. Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature. J Neurosci 2014; 34: 7988-7998. doi: 10.1523/jneurosci.0777-14.2014 PMID: 24899720
30. Schaeffer V, Lavenir I, Ozcelik S, Tolnay M, Winkler DT, Goedert M. Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy. Brain 2012; 135: 2169-2177. doi: 10.1093/brain/aws143 PMID: 22689910
31. Jiang T, Yu JT, Zhu XC, Zhang QQ, Cao L, Wang HF, et al. Temsirolimus attenuates tauopathy in vitro and in vivo by targeting hyperphosphorylation and autophagic clearance. Neuropharmacology 2014; 85: 121-130. doi: 10.1016/j.neuropharm.2014.05.032 PMID: 24880087
32. Siman R, Lin Y-G, Malthankar-Phatak G, Dong Y. A rapid gene delivery-based mouse model for earlystage Alzheimer disease-type tauopathy. J Neuropathol Exp Neurol 2013; 72: 1062-1071. doi: 10. 1097/NEN.0000000000000006 PMID: 24128676
33. Siman R, Salidas S. Gamma-secretase subunit composition and distribution in the presenilin wild-type and mutant mouse brain. Neuroscience 2004; 129: 615-628. doi: 10.1016/j.neuroscience.2004.08. 028 PMID: 15541883
34. Zhang C, McNeil E, Dressler L, Siman R. Long-lasting impairment in hippocampal neurogenesis associated with amyloid deposition in a knock-in mouse model of familial Alzheimer's disease. Exp Neurol 2007; 204: 77-87. doi: 10.1097/NEN.0000000000000006 PMID: 17070803
35. Timm F. Histochemie des Ammonshorn-gebietes. Z Zellforsch 1958; 46: 548-553.
36. Coleman PD, Flood DG, West MJ. Volume of the components of the hippocampus in the aging F344 rat. J Comp Neurol 1987; 266: 300-306. PMID: 3437077
37. Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ. Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. J Neurosci 2008; 28: 5422-5432. doi: 10. 1523/JNEUROSCI.0955-08.2008 PMID: 18495876
38. Spilman P, Podlutskaya N, Hart MJ, Debnath J, Gorostiza O, Bredesen D, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One 2010; 5: e9979. doi: 10.1371/journal.pone.0009979 PMID: 20376313
39. Viscomi MT, D'Amelio M, Cavallucci V, Latini L, Bisicchia E, Nazio F, et al. Stimulation of autophagy by rapamycin protects neurons from remote degeneration after acute focal cerebral ischemia. Autophagy 2012; 8: 222-235. doi: 10.4161/auto.8.2.18599 PMID: 22248716
40. Cortes CJ, Qin K, Cook J, Solanki A, Mastrianni JA. Rapamycin delays disease onset and prevents PrP plaque deposition in a mouse model of Gerstmann-Straussler-Scheinker disease. J Neurosci 2012; 32: 12396-12405. doi: 10.1523/JNEUROSCI.6189-11.2012 PMID: 22956830
41. Bove J, Martinez-Vicente M, Vila M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat Rev Neurosci 2011; 12: 437-452. doi: 10.1038/nrn3068 PMID: 21772323
42. Page G, Khidir FA, Pain S, Umaerus M, O'Donnell TA, Cooper NJ, et al. Group I metabotropic glutamate receptors activate the p70S6 kinase via both mTOR and ERK1/2 signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int 2006; 49: 413-421. doi: 10.1016/j.neuint.2006. 01.020 PMID: 16549223
43. McLeland CB, Rodriguez J, Stern ST. Autophagy monitoring assay: qualitative analysis of MAP LC3-I to II conversion by immunoblot. Methods Mol. Biol. 2011; 697: 199-206. doi: 10.1007/978-1-60327-198-1-21 PMID: 21116969
44. Gertig U, Hanisch UK. Microglial diversity by responses and responders. Front. Cell. Neurosci. 2014; 8: 101. doi: 10.3389/fncel.2014.00101 PMID: 24744702
45. Eddleston M, Mucke L. Molecular profile of reactive astrocytes-implications for their role in neurologic disease. Neuroscience 1993; 54: 15-36. PMID: 8515840
46. Matthews DA, Cotman C, Lynch G. An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat: II. Reappearance of morphologically normal synaptic contacts. Brain Res 1976; 115: 23-41. PMID: 974742
47. Akiyama H, McGeer PL. Brain microglia constitutively express beta-2 integrins. J Neuroimmunol 1990; 30: 81-93. PMID: 1977769
48. McGeer EG, McGeer PL. Inflammatory processes in Alzheimer's disease. Prog. Neuropychopharmacol. Biol. Psychiatry 2003; 27: 741-749. doi: 10.1016/S0278-5846(03)00124-6
49. Jaturapatporn D, Isaac MG, McCleery J, Tabet N. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer's disease. Chchrane Database Syst. Rev. 2012; 2: CD006378. doi: 10.1002/14651858.CD006378.pub2
50. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015; 14: 388-405. doi: 10.1016/S1474-4422(15)70016-5 PMID: 25792098
51. Ravikumar B, Vacher C, Berger Z. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat Genet 2004; 36: 585-595. doi: 10.1038/ng1362 PMID: 15146184
52. Dehay B, Bove J, Rodriguez-Muela N, Perier C, Recasens A, Boya P, Vila M. Pathogenic lysosomal depletion in Parkinson's disease. J Neurosci 2010; 30: 12535-12544. doi: 10.1523/jneurosci.1920-10. 2010 PMID: 20844148
53. Menzies FM, Heubener J, Renna M, Bonin M, Riess O, Rubinsztein DC. Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3. Brain 2010; 133: 93-104. doi: 10.1093/brain/awp292 PMID: 20007218
54. Wang IF, Guo BS, Liu YC, Wu CC, Yang CH, Tsai KJ, Shen CK. Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proc Natl Acad Sci USA 2012; 109: 15024-15029. doi: 10.1073/pnas.1206362109 PMID: 22932872
55. Nixon RA, Yang DS. Autophagy failure in Alzheimer's disease-locating the primary defect. Neurobiol Dis 2011; 43: 38-45. doi: 10.1016/j.nbd.2011.01.021 PMID: 21296668
56. Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR. Selective inhibition of Alzheimer diseaselike tau aggregation by phenothiazines. Proc Natl Acad Sci USA 1996; 93: 11213-11218. PMID: 8855335
57. Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 2004; 10: 148-154. doi: 10.1038/nm985 PMID: 14730359
58. Spires TL, Orne JD, SantaCruz K, Pitstick R, Carlson GA, Ashe KH, Hyman BT. Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol 2006; 168: 1598-1607. doi: 10.2353/ajpath.2006.050840 PMID: 16651626
59. Ward S.M., Himmelstein D.S., Lancia J.K., Binder L.I. Tau oligomers and tau toxicity in neurodegenerative disease. Biochem Soc Trans 2012; 40: 667-671. doi: 10.1042/BST/20120134 PMID: 22817713