Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1

BMC Neurology

Volumn 13, Issue , 2013, Pages

  Mainberger, Florian ^a   Jung, Nikolai H ^a   Zenker, Martin ^b   Wahlländer, Ute ^c   Freudenberg, Leonie ^h   Langer, Susanne ^a   Berweck, Steffen ^d   Winkler, Tobias ^c   Straube, Andreas ^c   Heinen, Florian ^e   Granström, Sofia ^f   Mautner, Victor Felix ^f   Lidzba, Karen ^g   Mall, Volker ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^c UNIVERSITY OF MUNICH   (Germany)

^d Schon Klinik Vogtareuth   (Germany)

^e LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^f UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^g UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^h UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Attention; Developmental disorder; Long term potentiation (LTP); Lovastatin; NF1; Paired associative stimulation (PAS); RAS pathway; Synaptic plasticity; Transcranial magnetic stimulation (TMS)

Indexed keywords

MEVINOLIN; PLACEBO;

ABSENCE OF SIDE EFFECTS; ADULT; ALERTNESS; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; EVOKED MUSCLE RESPONSE; FEMALE; HUMAN; MALE; NERVE CELL PLASTICITY; NEUROFIBROMATOSIS; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TRANSCRANIAL MAGNETIC STIMULATION;

ADULT; ANTICHOLESTEREMIC AGENTS; ATTENTION; CEREBRAL CORTEX; COHORT STUDIES; DECISION MAKING; DOUBLE-BLIND METHOD; EVOKED POTENTIALS, MOTOR; FEMALE; HUMANS; LONG-TERM POTENTIATION; LOVASTATIN; MALE; NEURAL INHIBITION; NEUROFIBROMATOSIS 1; TIME FACTORS; TRANSCRANIAL MAGNETIC STIMULATION; YOUNG ADULT;

EID: 84884873014     PISSN: None     EISSN: 14712377     Source Type: Journal    
DOI: 10.1186/1471-2377-13-131     Document Type: Article

References (46)

1. Basu TN, Gutmann DH, Fletcher JA, Glover TW, Collins FS, Downward J. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature 1992, 356(6371):713-715. 10.1038/356713a0, 1570015.
2. DeClue JE, Papageorge AG, Fletcher JA, Diehl SR, Ratner N, Vass WC, Lowy DR. Abnormal regulation of mammalian p21ras contributes to malignant tumor growth in von Recklinghausen (type 1) neurofibromatosis. Cell 1992, 69(2):265-273. 10.1016/0092-8674(92)90407-4, 1568246.
3. North K. Neurofibromatosis type 1. Am J Med Genet 2000, 97(2):119-127. 10.1002/1096-8628(200022)97:2<119::AID-AJMG3>3.0.CO;2-3, 11180219.
4. Shilyansky C, Lee YS, Silva AJ. Molecular and cellular mechanisms of learning disabilities: a focus on NF1. Annu Rev Neurosci 2010, 33:221-243. 10.1146/annurev-neuro-060909-153215, 3063104, 20345245.
5. Friedman JM. Epidemiology of neurofibromatosis type 1. Am J Med Genet 1999, 89(1):1-6. 10.1002/(SICI)1096-8628(19990326)89:1<1::AID-AJMG3>3.0.CO;2-8, 10469430.
6. Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology 2005, 65(7):1037-1044. 10.1212/01.wnl.0000179303.72345.ce, 16217056.
7. Mautner VF, Kluwe L, Thakker SD, Leark RA. Treatment of ADHD in neurofibromatosis type 1. Dev Med Child Neurol 2002, 44(3):164-170. 10.1017/S0012162201001876, 12005317.
8. Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW, Cannon TD, Silva AJ. The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 2005, 15(21):1961-1967. 10.1016/j.cub.2005.09.043, 16271875.
9. Costa RM, Silva AJ. Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. J Child Neurol 2002, 17(8):622-626. 10.1177/088307380201700813, 12403561.
10. Silva AJ, Frankland PW, Marowitz Z, Friedman E, Laszlo GS, Cioffi D, Jacks T, Bourtchuladze R. A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 1997, 15(3):281-284. 10.1038/ng0397-281, 9054942.
11. Shilyansky C, Karlsgodt KH, Cummings DM, Sidiropoulou K, Hardt M, James AS, Ehninger D, Bearden CE, Poirazi P, Jentsch JD, et al. Neurofibromin regulates corticostriatal inhibitory networks during working memory performance. Proc Natl Acad Sci USA 2010, 107(29):13141-13146. 10.1073/pnas.1004829107, 2919968, 20624961.
12. Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ. Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 2008, 135(3):549-560. 10.1016/j.cell.2008.09.060, 2673196, 18984165.
13. Krab LC, de Goede-Bolder A, Aarsen FK, Pluijm SM, Bouman MJ, van der Geest JN, Lequin M, Catsman CE, Arts WF, Kushner SA, et al. Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial. JAMA 2008, 300(3):287-294. 10.1001/jama.300.3.287, 2664742, 18632543.
14. Acosta MT, Kardel PG, Walsh KS, Rosenbaum KN, Gioia GA, Packer RJ. Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study. Pediatr Neurol 2011, 45(4):241-245. 10.1016/j.pediatrneurol.2011.06.016, 21907886.
15. Rioult-Pedotti MS, Friedman D, Hess G, Donoghue JP. Strengthening of horizontal cortical connections following skill learning. Nat Neurosci 1998, 1(3):230-234. 10.1038/678, 10195148.
16. Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 2004, 5(3):173-183.
17. Guilding C, McNair K, Stone TW, Morris BJ. Restored plasticity in a mouse model of neurofibromatosis type 1 via inhibition of hyperactive ERK and CREB. Eur J Neurosci 2007, 25(1):99-105. 10.1111/j.1460-9568.2006.05238.x, 17241271.
18. Cooke SF, Bliss TV. Plasticity in the human central nervous system. Brain 2006, 129(Pt 7):1659-1673.
19. Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 2000, 123(Pt 3):572-584.
20. Stefan K, Kunesch E, Benecke R, Cohen LG, Classen J. Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J Physiol 2002, 543(Pt 2):699-708. 2290505, 12205201.
21. Delvendahl I, Jung NH, Mainberger F, Kuhnke NG, Cronjaeger M, Mall V. Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex. Clin Neurophysiol 2010, 121(4):594-602. 10.1016/j.clinph.2009.09.034, 20074998.
22. Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 1994, 117(Pt 4):847-858.
23. Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD. Corticocortical inhibition in human motor cortex. J Physiol 1993, 471:501-519. 1143973, 8120818.
24. Battaglia F, Wang HY, Ghilardi MF, Gashi E, Quartarone A, Friedman E, Nixon RA. Cortical plasticity in Alzheimer's disease in humans and rodents. Biol Psychiatry 2007, 62(12):1405-1412. 10.1016/j.biopsych.2007.02.027, 17651702.
25. Frantseva MV, Fitzgerald PB, Chen R, Moller B, Daigle M, Daskalakis ZJ. Evidence for impaired long-term potentiation in schizophrenia and its relationship to motor skill learning. Cereb Cortex 2008, 18(5):990-996. 10.1093/cercor/bhm151, 17855721.
26. Battaglia F, Quartarone A, Rizzo V, Ghilardi MF, Di Rocco A, Tortorella G, Girlanda P. Early impairment of synaptic plasticity in patients with Down's syndrome. Neurobiol Aging 2008, 29(8):1272-1275. 10.1016/j.neurobiolaging.2007.02.025, 17399853.
27. Bagnato S, Agostino R, Modugno N, Quartarone A, Berardelli A. Plasticity of the motor cortex in Parkinson's disease patients on and off therapy. Mov Disord 2006, 21(5):639-645. 10.1002/mds.20778, 16353175.
28. Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ. Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 2002, 415(6871):526-530. 10.1038/nature711, 11793011.
29. Ziemann U, Muellbacher W, Hallett M, Cohen LG. Modulation of practice-dependent plasticity in human motor cortex. Brain 2001, 124(Pt 6):1171-1181.
30. Ziemann U, Siebner HR. Modifying motor learning through gating and homeostatic metaplasticity. Brain Stimul 2008, 1(1):60-66. 10.1016/j.brs.2007.08.003, 20633369.
31. Russmann H, Lamy JC, Shamim EA, Meunier S, Hallett M. Associative plasticity in intracortical inhibitory circuits in human motor cortex. Clin Neurophysiol 2009, 120(6):1204-1212. 10.1016/j.clinph.2009.04.005, 2726953, 19435676.
32. Tobert JA, Hitzenberger G, Kukovetz WR, Holmes IB, Jones KH. Rapid and substantial lowering of human serum cholesterol by mevinolin (MK-803), an inhibitor of hydroxymethylglutaryl-coenzyme a reductase. Atherosclerosis 1982, 41(1):61-65. 10.1016/0021-9150(82)90070-3, 6918220.
33. Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009, 120(12):2008-2039. 10.1016/j.clinph.2009.08.016, 3260536, 19833552.
34. Brasil-Neto JP, Cohen LG, Panizza M, Nilsson J, Roth BJ, Hallett M. Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity. J Clin Neurophysiol 1992, 9(1):132-136. 10.1097/00004691-199201000-00014, 1552001.
35. Kaneko K, Kawai S, Fuchigami Y, Morita H, Ofuji A. The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain. Electroencephalogr Clin Neurophysiol 1996, 101(6):478-482.
36. Jung NH, Delvendahl I, Kuhnke NG, Hauschke D, Stolle S, Mall V. Navigated transcranial magnetic stimulation does not decrease the variability of motor-evoked potentials. Brain Stimul 2010, 3(2):87-94. 10.1016/j.brs.2009.10.003, 20633437.
37. Awiszus F. TMS and threshold hunting. Suppl Clin Neurophysiol 2003, 56:13-23.
38. Mishory A, Molnar C, Koola J, Li X, Kozel FA, Myrick H, Stroud Z, Nahas Z, George MS. The maximum-likelihood strategy for determining transcranial magnetic stimulation motor threshold, using parameter estimation by sequential testing is faster than conventional methods with similar precision. JECT 2004, 20(3):160-165.
39. Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, Dimitrijevic MR, Hallett M, Katayama Y, Lucking CH, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 1994, 91(2):79-92. 10.1016/0013-4694(94)90029-9, 7519144.
40. Muellbacher W, Ziemann U, Wissel J, Dang N, Kofler M, Facchini S, Boroojerdi B, Poewe W, Hallett M. Early consolidation in human primary motor cortex. Nature 2002, 415(6872):640-644. 10.1038/nature712, 11807497.
41. Stefan K, Wycislo M, Classen J. Modulation of associative human motor cortical plasticity by attention. J Neurophysiol 2004, 92(1):66-72. 10.1152/jn.00383.2003, 14724259.
42. Peurala SH, Muller-Dahlhaus JF, Arai N, Ziemann U. Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). Clin Neurophysiol 2008, 119(10):2291-2297. 10.1016/j.clinph.2008.05.031, 18723394.
43. Orth M, Snijders AH, Rothwell JC. The variability of intracortical inhibition and facilitation. Clin Neurophysiol 2003, 114(12):2362-2369. 10.1016/S1388-2457(03)00243-8, 14652096.
44. Stinear CM, Byblow WD. Elevated threshold for intracortical inhibition in focal hand dystonia. Mov Disord 2004, 19(11):1312-1317. 10.1002/mds.20160, 15390002.
45. Zimmermann P, Fimm B. Testbatterie zur Aufmerksamkeitsprüfung [Testbattery of Attentional Performance (TAP)] version 1.7 2002, Herzogenrath: Psytest.
46. Igel M, Sudhop T, von BK. Pharmacology of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), including rosuvastatin and pitavastatin. J Clin Pharmacol 2002, 42(8):835-845. 10.1177/009127002401102731, 12162466.