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Molekularbiologische Aspekte der Neuroplastizität

Ansätze für die Therapie bei Tinnitus und Hörstörungen

Molecular biological aspects of neuroplasticity

Approaches for treating tinnitus and hearing disorders

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Zusammenfassung

Neuronale Plastizität ist die Fähigkeit des Gehirns, seine Struktur und Organisation veränderten biologischen Anforderungen anzupassen. Kortikale Plastizität heißt, dass sich Größe, Konnektivität oder Aktivierungsmuster kortikaler Netzwerke aktivitätsabhängig ändern. Synaptische Plastizität bedeutet, dass sich die Stärke der synaptischen Übertragung aktivitätsabhängig ändert. Die zunehmende Stimulation afferenter Fasern führt zu lang anhaltenden Veränderungen der synaptischen Übertragung im Sinne einer Langzeitpotenzierung („long-term potentiation“, LTP), die verringerte Stimulation zur Langzeitdepression („long-term depression“, LTD). Letztendlich führen Schäden der Haarzellen, des Hörnervs und Exzitotoxizität zur Dysbalance zwischen LTP und LTD und damit zur Änderung der synaptischen Plastizität. Die Dysbalance zwischen LTP und LTD führt zur Veränderung der Genexpression und somit der Neurotransmission, der Rezeptoren, Ionenkanäle, regulatorischen Enzyme sowie zu direkten Veränderungen der Synapsen. Dies verursacht eine Zunahme der Erregung auf zellulärer Ebene. In der Folge kann die Dysbalance zu einer Hyperaktivität im dorsalen cochleären Nukleus, im Colliculus inferior sowie im auditorischen Kortex und im weiteren Verlauf über die Veränderung der kortikalen Plastizität zu Tinnitus führen.

Abstract

Peripheral and central structures are involved in the onset of tinnitus. Neuronal plasticity is of special importance for the occurrence of central tinnitus and its persistent form. Neuronal plasticity is the ability of the brain to adapt its own structure (synapses, nerve cells, or even whole areas of the brain) and its organization to modified biological requirements. Neuroplasticity is an ongoing dynamic process. Generally speaking, there are two types of plasticity: synaptic and cortical. Cortical plasticity involves activity-dependent changes in size, connectivity, or in the activation pattern of cortical networks. Synaptic plasticity refers to the activity-dependent change in the strength of synaptic transmission and can affect both the morphology and physiology of the synapse. The stimulation of afferent fibers leads to long-lasting changes in synaptic transmission. This phenomenon is called long-term potentiation (LTP) or long-term depression (LTD). From the perspective of molecular biology, synaptic plasticity is of particular importance for the development of tinnitus and its persistence. Ultimately, the damage to the hair cells, auditory nerve, and excitotoxicity results in an imbalance between LTP and LTD and thus in changes of synaptic plasticity. After excessive acoustic stimulation, LTP can be induced by the increase of afferent inputs, whereas decreased afferent inputs generate LTD. The imbalance between LTP and LTD leads to changes in gene expression and involves changes in neurotransmission, in the expression of the receptors, ion channels, regulatory enzymes, and in direct changes on the synapses. This causes an increase of activity on the cellular level. As a result, the imbalance can lead to hyperactivity in the dorsal cochlear nucleus, inferior colliculus, and in the auditory cortex and, later on, to changes in cortical plasticity leading to tinnitus.

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Authors and Affiliations

  1. HNO-Klinik und Poliklinik, Tinnituszentrum und molekularbiologisches Forschungslabor, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Deutschland

    B. Mazurek, H. Haupt, J. Gross & A.J. Szczepek

  2. HNO-Klinik, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Deutschland

    H. Olze

  3. Medizinische Klinik mit Schwerpunkt für Psychosomatik, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Deutschland

    B.F. Klapp

  4. Klinik für Psychiatrie und Psychotherapie, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Deutschland

    M. Adli

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Mazurek, B., Olze, H., Haupt, H. et al. Molekularbiologische Aspekte der Neuroplastizität. HNO 58, 973–982 (2010). https://doi.org/10.1007/s00106-010-2177-8

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