Publikationsserver der Universitätsbibliothek Marburg
Titel:The absence of a functional thymus is associated with alterations in peripheral and central neurotransmitters and neurotrophins
Autor:Jouda, Jamela Aesa Kahdem
Weitere Beteiligte: Bauer, Uta-Maria (Prof. Dr. )
Veröffentlicht:2012
URI:https://archiv.ub.uni-marburg.de/diss/z2013/0001
URN: urn:nbn:de:hebis:04-z2013-00015
DOI: https://doi.org/10.17192/z2013.0001
DDC: Medizin
Titel (trans.):The absence of a functional thymus is associated with alterations in peripheral and central neurotransmitters and neurotrophins
Publikationsdatum:2013-02-22
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Thymus, Unde mice, Neurotrophins, BDNF, Thymus, Unde mice, NGF, Neurotrophins, Neurotransmitters, NA, Neurotransmitters, NA, NGF, BDNF

Summary:
Physiologische Wechselwirkungen zwischen neuronalem, endokrinem und Immunsystem sind inzwischen gut belegt. Diese Arbeit befasst sich mit Auswirkungen des Fehlens von funktionsfähigem Thymus auf Neurotransmitter- und Neurotrophin-Konzentrationen in der Milz sowie bestimmten Hirnregionen unter Verwendung homozygoter Foxn1nu Mäuse als Modell. Diese Spontanmutation führt zu einer fehlerhaften Entwicklung der Thymusanlage mit Ausbleiben der Entwicklung reifer T-Zellen. Der erste Teil der Arbeit zeigt bei Foxn1nu Mäusen 1) eine verstärkte sympathische Innervation der Milz, die auch im Erwachsenalter anhält; 2) Änderungen noradrenerger und serotonerger Neurotransmitter in bestimmten Hirnregionen, vergleichbar denen in der Milz; 3) eine erhöhte Dichte noradrenerger Fasern in Milz und Hypothalamus; 4) eine Erhöhung der Konzentrationen des Wachstumsfaktors „brain-derived nerve growth factor“ (BDNF) und von Neurotrophin-3 (NT-3) sowie von BDNF-Signalen in Milz und Hippocampus; 5) ausgeprägte anatomische Änderungen des Hippocampus und 6) erhöhte Kortikosteron-Blutwerte. Diese Änderungen verschwinden nach Rekonstitution der Foxn1nu Mäuse durch Thymustransplantation bei Geburt. Der zweite Teil geht der Frage nach, ob diese Änderungen in athymischen Mäusen grundsätzlicher bedeuten, dass das catecholaminerge System ursächlich mit der Neurotrophinbildung in Verbindung steht. Die Befunde zeigen, dass die Zerstörung noradrenerger Neurone nach Neurotoxinapplikation zu einer dauerhaften oder vorübergehenden Denervierung führt, begleitet von zu- oder abnehmenden Kortikosteron-Blutspiegeln sowie Neurotrophin-Konzentrationen in Milz und Gehirn, abhängig vom Alter der Denervierung. Zusammengenommen weisen die hier vorgelegten Ergebnisse darauf hin, dass die bei Foxn1nu Mäusen gefundenen Änderungen an Neurotransmittern und Neurotrophinen kein Epiphänomen darstellen, das zufällig mit dem Fehlen der Thymusfunktion einhergeht, sondern dass wahrscheinlich reife T-Zellen direkt oder indirekt eine inhibitorische Wirkung auf die Entwicklung der sympathischen Milzinnervation sowie auf catecholaminerge und serotonerge Mechanismen des zentralen Nervensystems entfalten. Die Ergebnisse liefern somit neue Belege, dass das Immunsystem nervale und endokrine Systeme beeinflussen kann.

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