nach oben

Journal of Neural Transmission

Erschienen in:

26.08.2016 | Psychiatry and Preclinical Psychiatric Studies - Review Article

Impaired synaptic plasticity in RASopathies: a mini-review

verfasst von: Florian Mainberger, Susanne Langer, Volker Mall, Nikolai H. Jung

Erschienen in: Journal of Neural Transmission | Ausgabe 10/2016

Einloggen, um Zugang zu erhalten

Abstract

Synaptic plasticity in the form of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological correlate of learning and memory. Impairments are discussed to be one of the underlying pathophysiological mechanisms of developmental disorders. In so-called RASopathies [e.g., neurofibromatosis 1 (NF1)], neurocognitive impairments are frequent and are affected by components of the RAS pathway which lead to impairments in synaptic plasticity. Transcranial magnetic stimulation (TMS) provides a non-invasive method to investigate synaptic plasticity in humans. Here, we review studies using TMS to evaluate synaptic plasticity in patients with RASopathies. Patients with NF1 and Noonan syndrome (NS) showed reduced cortical LTP-like synaptic plasticity. In contrast, increased LTP-like synaptic plasticity has been shown in Costello syndrome. Notably, lovastatin normalized impaired LTP-like plasticity and increased intracortical inhibition in patients with NF1. TMS has been shown to be a safe and efficient method to investigate synaptic plasticity and intracortical inhibition in patients with RASopathies. Deeper insights in impairments of synaptic plasticity in RASopathies could help to develop new options for the therapy of learning deficits in these patients.

Acosta MT, Kardel PG, Walsh KS, Rosenbaum KN, Gioia GA, Packer RJ (2011) Lovastatin as treatment for neurocognitive deficits in neurofibromatosis type 1: phase I study. Pediatr Neurol 45(4):241–245CrossRefPubMed

Bagnato S, Agostino R, Modugno N, Quartarone A, Berardelli A (2006) Plasticity of the motor cortex in Parkinson’s disease patients on and off therapy. Mov Disord Off J Mov Disord Soc 21(5):639–645. doi:10.1002/mds.20778 CrossRef

Battaglia F, Wang HY, Ghilardi MF, Gashi E, Quartarone A, Friedman E, Nixon RA (2007) Cortical plasticity in Alzheimer’s disease in humans and rodents. Biol Psychiatry 62(12):1405–1412. doi:10.1016/j.biopsych.2007.02.027 CrossRefPubMed

Belvisi D, Suppa A, Marsili L, Di Stasio F, Parvez AK, Agostino R, Fabbrini G, Berardelli A (2013) Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia. Exp Neurol 240:64–74. doi:10.1016/j.expneurol.2012.11.003 CrossRefPubMed

Berardelli A, Rothwell JC, Hallett M, Thompson PD, Manfredi M, Marsden CD (1998) The pathophysiology of primary dystonia. Brain 121(Pt 7):1195–1212CrossRefPubMed

Bezniakow N, Gos M, Obersztyn E (2014) The RASopathies as an example of RAS/MAPK pathway disturbances—clinical presentation and molecular pathogenesis of selected syndromes. Dev Period Med 18(3):285–296PubMed

Citri A, Malenka RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 33(1):18–41CrossRefPubMed

Classen J, Wolters A, Stefan K, Wycislo M, Sandbrink F, Schmidt A, Kunesch E (2004) Paired associative stimulation. Suppl Clin Neurophysiol 57:563–569CrossRefPubMed

Costa RM, Silva AJ (2002) Molecular and cellular mechanisms underlying the cognitive deficits associated with neurofibromatosis 1. J Child Neurol 17(8):622–626CrossRefPubMed

Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ (2002) Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1. Nature 415(6871):526–530CrossRefPubMed

Cui Y, Costa RM, Murphy GG, Elgersma Y, Zhu Y, Gutmann DH, Parada LF, Mody I, Silva AJ (2008) Neurofibromin regulation of ERK signaling modulates GABA release and learning. Cell 135(3):549–560CrossRefPubMedPubMedCentral

Delvendahl I, Kuhnke NG, Jung NH, Mainberger F, Cronjaeger M, Unterrainer J, Hauschke D, Mall V (2011) The time course of motor cortex plasticity after spaced motor practice. Brain Stimul 4(3):156–164CrossRefPubMed

Dileone M, Profice P, Pilato F, Alfieri P, Cesarini L, Mercuri E, Leoni C, Tartaglia M, Di Iorio R, Zampino G, Di Lazzaro V (2010) Enhanced human brain associative plasticity in Costello syndrome. J Physiol 588(Pt 18):3445–3456. doi:10.1113/jphysiol.2010.191072 CrossRefPubMedPubMedCentral

Dileone M, Zampino G, Profice P, Pilato F, Leoni C, Ranieri F, Capone F, Tartaglia M, Brown P, Di Lazzaro V (2012) Dystonia in Costello syndrome. Parkinsonism Relat Disord 18(6):798–800. doi:10.1016/j.parkreldis.2012.03.015 CrossRefPubMed

Fierro B, Piazza A, Brighina F, La Bua V, Buffa D, Oliveri M (2001) Modulation of intracortical inhibition induced by low- and high-frequency repetitive transcranial magnetic stimulation. Exp Brain Res 138(4):452–457CrossRefPubMed

Flavell SW, Greenberg ME (2008) Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system. Annu Rev Neurosci 31:563–590CrossRefPubMedPubMedCentral

Frantseva MV, Fitzgerald PB, Chen R, Moller B, Daigle M, Daskalakis ZJ (2008) Evidence for impaired long-term potentiation in schizophrenia and its relationship to motor skill learning. Cereb Cortex 18(5):990–996. doi:10.1093/cercor/bhm151 CrossRefPubMed

Ghilardi MF, Carbon M, Silvestri G, Dhawan V, Tagliati M, Bressman S, Ghez C, Eidelberg D (2003) Impaired sequence learning in carriers of the DYT1 dystonia mutation. Ann Neurol 54(1):102–109CrossRefPubMed

Jung NH, Janzarik WG, Delvendahl I, Munchau A, Biscaldi M, Mainberger F, Baumer T, Rauh R, Mall V (2013) Impaired induction of long-term potentiation-like plasticity in patients with high-functioning autism and Asperger syndrome. Dev Med Child Neurol 55(1):83–89. doi:10.1111/dmcn.12012 CrossRefPubMed

Krab LC, de Goede-Bolder A, Aarsen FK, Pluijm SM, Bouman MJ, van der Geest JN, Lequin M, Catsman CE, Arts WF, Kushner SA, Silva AJ, de Zeeuw CI, Moll HA, Elgersma Y (2008) Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial. JAMA 300(3):287–294CrossRefPubMedPubMedCentral

Kratz CP, Niemeyer CM, Zenker M (2007) An unexpected new role of mutant Ras: perturbation of human embryonic development. J Mol Med 85(3):227–235CrossRefPubMedPubMedCentral

Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519CrossRefPubMedPubMedCentral

Lee YS, Ehninger D, Zhou M, Oh JY, Kang M, Kwak C, Ryu HH, Butz D, Araki T, Cai Y, Balaji J, Sano Y, Nam CI, Kim HK, Kaang BK, Burger C, Neel BG, Silva AJ (2014) Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome. Nat Neurosci 17(12):1736–1743. doi:10.1038/nn.3863 CrossRefPubMedPubMedCentral

Li W, Cui Y, Kushner SA, Brown RA, Jentsch JD, Frankland PW, Cannon TD, Silva AJ (2005) The HMG-CoA reductase inhibitor lovastatin reverses the learning and attention deficits in a mouse model of neurofibromatosis type 1. Curr Biol 15(21):1961–1967CrossRefPubMed

Lynch MA (2004) Long-term potentiation and memory. Physiol Rev 84(1):87–136CrossRefPubMed

Mainberger F, Jung NH, Zenker M, Wahllander U, Freudenberg L, Langer S, Berweck S, Winkler T, Straube A, Heinen F, Granstrom S, Mautner VF, Lidzba K, Mall V (2013a) Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1. BMC Neurol 13:131. doi:10.1186/1471-2377-13-131 CrossRefPubMedPubMedCentral

Mainberger F, Zenker M, Jung NH, Delvendahl I, Brandt A, Freudenberg L, Heinen F, Mall V (2013b) Impaired motor cortex plasticity in patients with Noonan syndrome. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 124(12):2439–2444. doi:10.1016/j.clinph.2013.04.343 CrossRef

Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1):5–21. doi:10.1016/j.neuron.2004.09.012 CrossRefPubMed

McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABAB receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173(1):86–93CrossRefPubMed

Oberman L, Ifert-Miller F, Najib U, Bashir S, Woollacott I, Gonzalez-Heydrich J, Picker J, Rotenberg A, Pascual-Leone A (2010) Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile × syndrome and autism spectrum disorder. Front Synaptic Neurosci 2:26. doi:10.3389/fnsyn.2010.00026 PubMedPubMedCentral

Pascual-Leone A, Valls-Sole J, Wassermann EM, Hallett M (1994) Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117(Pt 4):847–858CrossRefPubMed

Quartarone A (2013) Transcranial magnetic stimulation in dystonia. Handb Clin Neurol 116:543–553. doi:10.1016/B978-0-444-53497-2.00043-7 CrossRefPubMed

Quartarone A, Pisani A (2011) Abnormal plasticity in dystonia: disruption of synaptic homeostasis. Neurobiol Dis 42(2):162–170. doi:10.1016/j.nbd.2010.12.011 CrossRefPubMed

Quartarone A, Siebner HR, Rothwell JC (2006) Task-specific hand dystonia: can too much plasticity be bad for you? Trends Neurosci 29(4):192–199CrossRefPubMed

Quartarone A, Morgante F, Sant’angelo A, Rizzo V, Bagnato S, Terranova C, Siebner HR, Berardelli A, Girlanda P (2008) Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia. J Neurol Neurosurg Psychiatry 79(9):985–990. doi:10.1136/jnnp.2007.121632 CrossRefPubMed

Rauen KA (2013) The RASopathies. Annu Rev Genom Hum Genet 14:355–369. doi:10.1146/annurev-genom-091212-153523 CrossRef

Rossi S, Hallett M, Rossini PM, Pascual-Leone A, Safety of TMSCG (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol Off J Int Fed Clin Neurophysiol 120(12):2008–2039. doi:10.1016/j.clinph.2009.08.016 CrossRef

Rothwell JC, Day BL, Thompson PD, Kujirai T (2009) Short latency intracortical inhibition: one of the most popular tools in human motor neurophysiology. J Physiol 587(Pt 1):11–12. doi:10.1113/jphysiol.2008.162461 CrossRefPubMedPubMedCentral

Shilyansky C, Karlsgodt KH, Cummings DM, Sidiropoulou K, Hardt M, James AS, Ehninger D, Bearden CE, Poirazi P, Jentsch JD, Cannon TD, Levine MS, Silva AJ (2010) Neurofibromin regulates corticostriatal inhibitory networks during working memory performance. Proc Natl Acad Sci USA 107(29):13141–13146CrossRefPubMedPubMedCentral

Silva AJ, Frankland PW, Marowitz Z, Friedman E, Laszlo GS, Cioffi D, Jacks T, Bourtchuladze R (1997) A mouse model for the learning and memory deficits associated with neurofibromatosis type I. Nat Genet 15(3):281–284CrossRefPubMed

Stefan K, Kunesch E, Cohen LG, Benecke R, Classen J (2000) Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123(Pt 3):572–584CrossRefPubMed

Stefan K, Kunesch E, Benecke R, Cohen LG, Classen J (2002) Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J Physiol 543(Pt 2):699–708CrossRefPubMedPubMedCentral

Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5(3):173–183CrossRefPubMed

Tidyman WE, Rauen KA (2009) The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev 19(3):230–236. doi:10.1016/j.gde.2009.04.001 CrossRefPubMedPubMedCentral

van der Vaart T, Plasschaert E, Rietman AB, Renard M, Oostenbrink R, Vogels A, de Wit MC, Descheemaeker MJ, Vergouwe Y, Catsman-Berrevoets CE, Legius E, Elgersma Y, Moll HA (2013) Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet Neurol 12(11):1076–1083. doi:10.1016/S1474-4422(13)70227-8 CrossRefPubMed

Weise D, Schramm A, Beck M, Reiners K, Classen J (2011) Loss of topographic specificity of LTD-like plasticity is a trait marker in focal dystonia. Neurobiol Dis 42(2):171–176. doi:10.1016/j.nbd.2010.11.009 CrossRefPubMed

Ziemann U, Ilic TV, Pauli C, Meintzschel F, Ruge D (2004) Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex. J Neurosci 24(7):1666–1672CrossRefPubMed

Titel: Impaired synaptic plasticity in RASopathies: a mini-review
verfasst von: Florian Mainberger
Susanne Langer
Volker Mall
Nikolai H. Jung
Publikationsdatum: 26.08.2016
Verlag: Springer Vienna
Erschienen in: Journal of Neural Transmission / Ausgabe 10/2016
Print ISSN: 0300-9564
Elektronische ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-016-1609-3

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Schützt Olivenöl vor dem Tod durch Demenz?

10.05.2024 Morbus Alzheimer Nachrichten

Konsumieren Menschen täglich 7 Gramm Olivenöl, ist ihr Risiko, an einer Demenz zu sterben, um mehr als ein Vierten reduziert – und dies weitgehend unabhängig von ihrer sonstigen Ernährung. Dafür sprechen Auswertungen zweier großer US-Studien.

Bluttest erkennt Parkinson schon zehn Jahre vor der Diagnose

10.05.2024 Parkinson-Krankheit Nachrichten

Ein Bluttest kann abnorm aggregiertes Alpha-Synuclein bei einigen Menschen schon zehn Jahre vor Beginn der motorischen Parkinsonsymptome nachweisen. Mit einem solchen Test lassen sich möglicherweise Prodromalstadien erfassen und die Betroffenen früher behandeln.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Wartezeit nicht kürzer, aber Arbeit flexibler

Psychotherapie Medizin aktuell

Fünf Jahren nach der Neugestaltung der Psychotherapie-Richtlinie wurden jetzt die Effekte der vorgenommenen Änderungen ausgewertet. Das Hauptziel der Novellierung war eine kürzere Wartezeit auf Therapieplätze. Dieses Ziel wurde nicht erreicht, es gab jedoch positive Auswirkungen auf andere Bereiche.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2016

Effects of theta-rhythm transcranial alternating current stimulation (4.5 Hz-tACS) in patients with clozapine-resistant negative symptoms of schizophrenia: a case series

Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction

The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: a systematic review and meta-analysis

Transcranial direct current stimulation of the prefrontal cortex increases attention to visual target stimuli

Transcranial direct current stimulation of the prefrontal cortex reduces cue-reactivity in alcohol-dependent patients