Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 42, 2012, Pages

  Sanchez, Pascal E ^a,b   Zhu, Lei ^a,b   Verret, Laure ^a,b   Vossel, Keith A ^a,b   Orr, Anna G ^a,b   Cirrito, John R ^c   Devidze, Nino ^a   Ho, Kaitlyn ^a   Yu, Gui Qiu ^a   Palop, Jorge J ^a,b   Mucke, Lennart ^a,b  

^a GLADSTONE INSTITUTE OF NEUROLOGICAL DISEASE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Dementia; Epilepsy; Hyperexcitability; Plasticity; Therapy

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; ETHOSUXIMIDE; ETIRACETAM; GABAPENTIN; PHENYTOIN; PREGABALIN; VALPROIC ACID; VIGABATRIN;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COGNITIVE DEFECT; CONTROLLED STUDY; DRUG EFFICACY; DRUG MEGADOSE; ELECTROENCEPHALOGRAPHY; LEARNING DISORDER; MEMORY DISORDER; MOUSE; NERVE CELL NETWORK; NONHUMAN; PRIORITY JOURNAL; SPIKE WAVE; SYNAPSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANALYSIS OF VARIANCE; ANIMALS; ANTICONVULSANTS; BLOTTING, WESTERN; COGNITION; COGNITION DISORDERS; ELECTROENCEPHALOGRAPHY; HUMANS; IMMUNOHISTOCHEMISTRY; MAZE LEARNING; MICE; MICE, TRANSGENIC; NERVE NET; PIRACETAM; SYNAPSES;

EID: 84867645474     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1121081109     Document Type: Article

References (70)

1. Wimo A, Prince M (2010) World Alzheimer Report 2010: The Global Economic Impact of Dementia (Alzheimer's Disease International, London), pp 1-56.
2. Mucke L (2009) Neuroscience: Alzheimer's disease. Nature 461:895-897.
3. Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: From synapses toward neural networks. Nat Neurosci 13:812-818.
4. Golde TE, Schneider LS, Koo EH (2011) Anti-aβ therapeutics in Alzheimer's disease: The need for a paradigm shift. Neuron 69:203-213.
5. Huang Y, Mucke L (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148: 1204-1222.
6. Golde TE, Petrucelli L, Lewis J (2010) Targeting Abeta and tau in Alzheimer's disease, an early interim report. Exp Neurol 223:252-266.
7. Palop JJ, Mucke L (2009) Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 66:435-440.
8. Dickerson BC, et al. (2005) Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology 65:404-411. (Pubitemid 41099803)
9. Putcha D, et al. (2011) Hippocampal hyperactivation associated with cortical thinning in Alzheimer's disease signature regions in non-demented elderly adults. J Neurosci 31:17680-17688.
10. Sperling RA, et al. (2010) Functional alterations in memory networks in early Alzheimer's disease. Neuromolecular Med 12:27-43.
11. Celone KA, et al. (2006) Alterations inmemory networks inmild cognitive impairment and Alzheimer's disease: An independent component analysis. J Neurosci 26:10222-10231. (Pubitemid 44527415)
12. Palop JJ, et al. (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55:697-711. (Pubitemid 47321079)
13. Minkeviciene R, et al. (2009) Amyloid beta-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 29:3453-3462.
14. Vogt DL, et al. (2011) Abnormal neuronal networks and seizure susceptibility in mice overexpressing the APP intracellular domain. Neurobiol Aging 32:1725-1729.
15. Roberson ED, et al. (2011) Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease. J Neurosci 31:700-711.
16. Harris JA, et al. (2010) Transsynaptic progression of amyloid-β-induced neuronal dysfunction within the entorhinal-hippocampal network. Neuron 68:428-441.
17. Verret L, et al. (2012) Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149:708-721.
18. Bialer M, White HS (2010) Key factors in the discovery and development of new antiepileptic drugs. Nat Rev Drug Discov 9:68-82.
19. De Smedt T, Raedt R, Vonck K, Boon P (2007) Levetiracetam: Part II, the clinical profile of a novel anticonvulsant drug. CNS Drug Rev 13:57-78. (Pubitemid 46705269)
20. De Smedt T, Raedt R, Vonck K, Boon P (2007) Levetiracetam: The profile of a novel anticonvulsant drug-part I: Preclinical data. CNS Drug Rev 13:43-56. (Pubitemid 46697842)
21. Chin J, et al. (2005) Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer's disease. J Neurosci 25:9694-9703. (Pubitemid 41510910)
22. Roberson ED, et al. (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316:750-754. (Pubitemid 46717684)
23. Cheng IH, et al. (2007) Accelerating amyloid-β fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem 282:23818- 23828.
24. Harris JA, et al. (2010) Many neuronal and behavioral impairments in transgenic mouse models of Alzheimer's disease are independent of caspase cleavage of the amyloid precursor protein. J Neurosci 30:372-381.
25. Binnie CD (2003) Cognitive impairment during epileptiform discharges: Is it ever justifiable to treat the EEG? Lancet Neurol 2:725-730.
26. Kleen JK, Scott RC, Holmes GL, Lenck-Santini PP (2010) Hippocampal interictal spikes disrupt cognition in rats. Ann Neurol 67:250-257.
27. Cissé M, et al. (2011) Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469:47-52.
28. Palop JJ, et al. (2003) Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. Proc Natl Acad Sci USA 100:9572-9577. (Pubitemid 37033969)
29. Palop JJ, Chin J,Mucke L (2006) A network dysfunction perspective on neurodegenerative diseases. Nature 443:768-773. (Pubitemid 44622680)
30. Kamenetz F, et al. (2003) APP processing and synaptic function. Neuron 37: 925-937. (Pubitemid 36398299)
31. Cirrito JR, et al. (2005) Synaptic activity regulates interstitial fluid amyloid-β levels in vivo. Neuron 48:913-922. (Pubitemid 41814696)
32. Cirrito JR, et al. (2008) Endocytosis is required for synaptic activity-dependent release of amyloid-beta in vivo. Neuron 58:42-51. (Pubitemid 351467029)
33. Bero AW, et al. (2011) Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nat Neurosci 14:750-756.
34. Löscher W, Hönack D (2000) Development of tolerance during chronic treatment of kindled rats with the novel antiepileptic drug levetiracetam. Epilepsia 41:1499-1506.
35. Glien M, Brandt C, Potschka H, Löscher W (2002) Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia 43:350-357. (Pubitemid 34297172)
36. van Vliet EA, et al. (2008) Development of tolerance to levetiracetam in rats with chronic epilepsy. Epilepsia 49:1151-1159.
37. Löscher W, Schmidt D (2006) Experimental and clinical evidence for loss of effect (tolerance) during prolonged treatment with antiepileptic drugs. Epilepsia 47: 1253-1284. (Pubitemid 44200405)
38. Ben-Menachem E, Edrich P, Van Vleymen B, Sander JW, Schmidt B (2003) Evidence for sustained efficacy of levetiracetam as add-on epilepsy therapy. Epilepsy Res 53:57-64. (Pubitemid 36170171)
39. Koh MT, Haberman RP, Foti S, McCown TJ, Gallagher M (2010) Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology 35:1016-1025.
40. Wang XM, Bausch SB (2004) Effects of distinct classes of N-methyl-D-aspartate receptor antagonists on seizures, axonal sprouting and neuronal loss in vitro: Suppression by NR2B-selective antagonists. Neuropharmacology 47:1008-1020.
41. Maroso M, et al. (2010) Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med 16:413-419.
42. Li S, et al. (2011) Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 31:6627-6638.
43. Ziyatdinova S, et al. (2011) Spontaneous epileptiform discharges in a mouse model of Alzheimer's disease are suppressed by antiepileptic drugs that block sodium channels. Epilepsy Res 94:75-85.
44. Kwan P, Brodie MJ (2001) Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet 357:216-222. (Pubitemid 32108114)
45. Mendez M, Lim G (2003) Seizures in elderly patients with dementia: Epidemiology and management. Drugs Aging 20:791-803. (Pubitemid 37159597)
46. Cumbo E, Ligori LD (2010) Levetiracetam, lamotrigine, and phenobarbital in patients with epileptic seizures and Alzheimer's disease. Epilepsy Behav 17:461-466.
47. Lynch BA, et al. (2004) The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci USA 101:9861-9866. (Pubitemid 38869327)
48. Custer KL, Austin NS, Sullivan JM, Bajjalieh SM (2006) Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci 26:1303-1313. (Pubitemid 43237062)
49. Chang WP, Südhof TC (2009) SV2 renders primed synaptic vesicles competent for Ca2+ -induced exocytosis. J Neurosci 29:883-897.
50. Yang XF, Rothman SM (2009) Levetiracetam has a time- and stimulation-dependent effect on synaptic transmission. Seizure 18:615-619.
51. Meehan AL, Yang X, McAdams BD, Yuan L, Rothman SM (2011) A new mechanism for antiepileptic drug action: Vesicular entry may mediate the effects of levetiracetam. J Neurophysiol 106:1227-1239.
52. Ueda Y, et al. (2007) Effect of levetiracetam on molecular regulation of hippocampal glutamate and GABA transporters in rats with chronic seizures induced by amygdalar FeCl3 injection. Brain Res 1151:55-61. (Pubitemid 46709879)
53. Li S, et al. (2009) Soluble oligomers of amyloid β protein facilitate hippocampal longterm depression by disrupting neuronal glutamate uptake. Neuron 62:788-801.
54. Abramov E, et al. (2009) Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci 12:1567-1576.
55. Kabogo D, Rauw G, Amritraj A, Baker G, Kar S (2010) ß-amyloid- related peptides potentiate K+-evoked glutamate release from adult rat hippocampal slices. Neurobiol Aging 31:1164-1172.
56. Angehagen M, et al. (2003) Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons. Neuroreport 14:471-475. (Pubitemid 36337953)
57. Lyseng-Williamson KA (2011) Levetiracetam: A review of its use in epilepsy. Drugs 71: 489-514.
58. Supnet C, Bezprozvanny I (2010) The dysregulation of intracellular calcium in Alzheimer disease. Cell Calcium 47:183-189.
59. Bezprozvanny I (2009) Calcium signaling and neurodegenerative diseases. Trends Mol Med 15:89-100.
60. Sperling RA, et al. (2009) Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron 63:178-188.
61. Krakow K, et al. (1999) EEG-triggered functional MRI of interictal epileptiform activity in patients with partial seizures. Brain 122:1679-1688. (Pubitemid 29425671)
62. Bénar CG, et al. (2006) EEG-fMRI of epileptic spikes: Concordance with EEG source localization and intracranial EEG. Neuroimage 30:1161-1170.
63. Kobayashi E, et al. (2006) Temporal and extratemporal BOLD responses to temporal lobe interictal spikes. Epilepsia 47:343-354.
64. Bakker A, et al. (2012) Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron 74:467-474.
65. Rockenstein EM, et al. (1995) Levels and alternative splicing of amyloid β protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem 270:28257-28267.
66. Mucke L, et al. (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: Synaptotoxicity without plaque formation. J Neurosci 20:4050-4058. (Pubitemid 30365675)
67. Palop JJ, Mucke L, Roberson ED (2011) Quantifying biomarkers of cognitive dysfunction and neuronal network hyperexcitability in mouse models of Alzheimer's disease: Depletion of calcium-dependent proteins and inhibitory hippocampal remodeling. Methods Mol Biol 670:245-262.
68. Johnson-Wood K, et al. (1997) Amyloid precursor protein processing and A β42 deposition in a transgenic mouse model of Alzheimer disease. Proc Natl Acad Sci USA 94:1550-1555.
69. Cirrito JR, et al. (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci 23:8844-8853. (Pubitemid 37210896)
70. Verges DK, Restivo JL, Goebel WD, Holtzman DM, Cirrito JR (2011) Opposing synaptic regulation of amyloid-β metabolismbyNMDAreceptors in vivo. JNeurosci 31:11328-11337.