@article{MassihVehSchenkeetal.2023,
  author    = {Massih, Bita and Veh, Alexander and Schenke, Maren and Mungwa, Simon and Seeger, Bettina and Selvaraj, Bhuvaneish T. and Chandran, Siddharthan and Reinhardt, Peter and Sterneckert, Jared and Hermann, Andreas and Sendtner, Michael and L{\"u}ningschr{\"o}r, Patrick},
  title     = {A 3D cell culture system for bioengineering human neuromuscular junctions to model ALS},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {11},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2023.996952},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304161},
  year      = {2023},
  abstract  = {The signals that coordinate and control movement in vertebrates are transmitted from motoneurons (MNs) to their target muscle cells at neuromuscular junctions (NMJs). Human NMJs display unique structural and physiological features, which make them vulnerable to pathological processes. NMJs are an early target in the pathology of motoneuron diseases (MND). Synaptic dysfunction and synapse elimination precede MN loss suggesting that the NMJ is the starting point of the pathophysiological cascade leading to MN death. Therefore, the study of human MNs in health and disease requires cell culture systems that enable the connection to their target muscle cells for NMJ formation. Here, we present a human neuromuscular co-culture system consisting of induced pluripotent stem cell (iPSC)-derived MNs and 3D skeletal muscle tissue derived from myoblasts. We used self-microfabricated silicone dishes combined with Velcro hooks to support the formation of 3D muscle tissue in a defined extracellular matrix, which enhances NMJ function and maturity. Using a combination of immunohistochemistry, calcium imaging, and pharmacological stimulations, we characterized and confirmed the function of the 3D muscle tissue and the 3D neuromuscular co-cultures. Finally, we applied this system as an in vitro model to study the pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and found a decrease in neuromuscular coupling and muscle contraction in co-cultures with MNs harboring ALS-linked SOD1 mutation. In summary, the human 3D neuromuscular cell culture system presented here recapitulates aspects of human physiology in a controlled in vitro setting and is suitable for modeling of MND.},
  language  = {en}
}
@article{LueningschroerSlottaHeimannetal.2020,
  author    = {L{\"u}ningschr{\"o}r, Patrick and Slotta, Carsten and Heimann, Peter and Briese, Michael and Weikert, Ulrich M. and Massih, Bita and Appenzeller, Silke and Sendtner, Michael and Kaltschmidt, Christian and Kaltschmidt, Barbara},
  title     = {Absence of Plekhg5 Results in Myelin Infoldings Corresponding to an Impaired Schwann Cell Autophagy, and a Reduced T-Cell Infiltration Into Peripheral Nerves},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2020.00185},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207538},
  year      = {2020},
  abstract  = {Inflammation and dysregulation of the immune system are hallmarks of several neurodegenerative diseases. An activated immune response is considered to be the cause of myelin breakdown in demyelinating disorders. In the peripheral nervous system (PNS), myelin can be degraded in an autophagy-dependent manner directly by Schwann cells or by macrophages, which are modulated by T-lymphocytes. Here, we show that the NF-κB activator Pleckstrin homology containing family member 5 (Plekhg5) is involved in the regulation of both Schwann cell autophagy and recruitment of T-lymphocytes in peripheral nerves during motoneuron disease. Plekhg5-deficient mice show defective axon/Schwann cell units characterized by myelin infoldings in peripheral nerves. Even at late stages, Plekhg5-deficient mice do not show any signs of demyelination and inflammation. Using RNAseq, we identified a transcriptional signature for an impaired immune response in sciatic nerves, which manifested in a reduced number of CD4\(^+\) and CD8\(^+\) T-cells. These findings identify Plekhg5 as a promising target to impede myelin breakdown in demyelinating PNS disorders.},
  language  = {en}
}
@article{SendtnerDittrichHughesetal.1994,
  author    = {Sendtner, Michael and Dittrich, F. and Hughes, R. A. and Thoenen, H.},
  title     = {Actions of CNTF and neurotrophins on degenerating motoneurons : preclinical studies and clinical implications},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62939},
  year      = {1994},
  abstract  = {Spinal motoneurons innervating skeletal muscle were amongst the first neurons shown to require the presence of their target cells to develop appropriately. Isolated embryonie chick and rat motoneurons have been used to identify neurotrophic factors and cytokines capable of supporting the survival of developing motoneurons. Such factors include ciliary neurotrophic factor (CNTF), which is present physiologically in high amounts in myelinating Schwann cells of peripheral nerves, and brain-derived neurotrophic factor (BDNF) which is synthesized in skeletal muscle and, after peripheral nerve lesion. in Schwann cells. These factors have been further analyzed for their physiological significance in maintaining motoneuron function in vivo, and for their potential therapeutic usefulness in degenerative motoneuron disease. Both CNTF and BDNF are capable of rescuing injured facial motoneurons in newbom rats. Furthermore, CNTF prolongs survival and improves motor function of pmn mice, an animal model for degenerative motoneuron disease, by preventing degeneration of motoneuron axons and somata. Thus treatment of human motoneuron disease with neurotrophic factors should be possible, provided that rational means for application of these factors can be established considering also the appearance of potential side effects.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{vonCollenbergSchmittRuelickeetal.2019,
  author    = {von Collenberg, Cora R. and Schmitt, Dominique and R{\"u}licke, Thomas and Sendtner, Michael and Blum, Robert and Buchner, Erich},
  title     = {An essential role of the mouse synapse-associated protein Syap1 in circuits for spontaneous motor activity and rotarod balance},
  series = {Biology Open},
  volume    = {8},
  journal   = {Biology Open},
  doi       = {10.1242/bio.042366},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201986},
  pages     = {bio042366},
  year      = {2019},
  abstract  = {Synapse-associated protein 1 (Syap1) is the mammalian homologue of synapse-associated protein of 47 kDa (Sap47) in Drosophila. Genetic deletion of Sap47 leads to deficiencies in short-term plasticity and associative memory processing in flies. In mice, Syap1 is prominently expressed in the nervous system, but its function is still unclear. We have generated Syap1 knockout mice and tested motor behaviour and memory. These mice are viable and fertile but display distinct deficiencies in motor behaviour. Locomotor activity specifically appears to be reduced in early phases when voluntary movement is initiated. On the rotarod, a more demanding motor test involving control by sensory feedback, Syap1-deficient mice dramatically fail to adapt to accelerated speed or to a change in rotation direction. Syap1 is highly expressed in cerebellar Purkinje cells and cerebellar nuclei. Thus, this distinct motor phenotype could be due to a so-far unknown function of Syap1 in cerebellar sensorimotor control. The observed motor defects are highly specific since other tests in the modified SHIRPA exam, as well as cognitive tasks like novel object recognition, Pavlovian fear conditioning, anxiety-like behaviour in open field dark-light transition and elevated plus maze do not appear to be affected in Syap1 knockout mice.},
  language  = {en}
}
@techreport{LuettickenWegenkaYuanetal.1994,
  author    = {L{\"u}tticken, Claudia and Wegenka, Ursula M. and Yuan, Juping and Buschmann, Jan and Schindler, Chris and Ziemiecki, Andrew and Harpur, Alisa G. and Wilks, Andrew F. and Yasukawa, Kiyoshi and Taga, Tetsuya and Kishimoto, Tadamitsu and Barbieri, Giovanna and Sendtner, Michael and Pellegrini, Sandra and Heinrich, Peter C. and Horn, Friedemann},
  title     = {Association of transcription factor APRF and protein kinase JAK1 with the IL-6 signal transducer gp130},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42577},
  year      = {1994},
  abstract  = {Interleukin-6, leukemia inhibitory factor, oncostatin M. Interleukin-11, and cilialy neurotrophic factor bind to receptor complexes that share the signal transducer gp130. Upon binding, the ligands rapidly activate DNA binding of acute-phase response factor (APRF), a protein antigenicaly relaled to the p91 subunit of the interferon-stimulated gene factor-(ISGF-3a). These cytokines caused tyrosine phosphorylation of APRF and ISGF-3a p91. Protein kinases of the Jak family were also rapidly tyrosine phosphorylated, and both APRF and Jak1 associated with gp130. These data indicate that Jak family protein kinases may participate in IL-6 signaling and that APRF may be activated in a complex with gp130.},
  language  = {en}
}
@article{SendtnerThoenenHoltmannetal.1992,
  author    = {Sendtner, Michael and Thoenen, Hans and Holtmann, B. and Kohlbeck, R. and Barde, Y.-A.},
  title     = {Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42673},
  year      = {1992},
  abstract  = {Motoneurons innervating the skeletal musculature were among the first neurons shown to require the presence of their target cells to develop appropriatelyl,2. But the characterization of molecules allowing motoneuron survival has been difficult. Ciliary neurotrophic factor prevents the death of motoneurons3-6, but its gene is not expressed during development7. Although the presence of a neurotrophin receptor on developing motoneurons8-1O has suggested a role for neurotrophins, none could be shown to promote motoneuron survival in vitro3. We report here that brainderived neurotrophic factor can prevent the death of axotomized motoneurons in newborn rats, suggesting a role for this neurotrophin for motoneuron survival in vivo.},
  language  = {en}
}
@article{DuezelvanPraagSendtner2016,
  author    = {D{\"u}zel, Emrah and van Praag, Henriette and Sendtner, Michael},
  title     = {Can physical exercise in old age improve memory and hippocampal function?},
  series = {Brain},
  volume    = {139},
  journal   = {Brain},
  number    = {3},
  doi       = {10.1093/brain/awv407},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190721},
  pages     = {662-673},
  year      = {2016},
  abstract  = {Physical exercise can convey a protective effect against cognitive decline in ageing and Alzheimer's disease. While the long-term health-promoting and protective effects of exercise are encouraging, it's potential to induce neuronal and vascular plasticity in the ageing brain is still poorly understood. It remains unclear whether exercise slows the trajectory of normal ageing by modifying vascular and metabolic risk factors and/or consistently boosts brain function by inducing structural and neurochemical changes in the hippocampus and related medial temporal lobe circuitry—brain areas that are important for learning and memory. Hence, it remains to be established to what extent exercise interventions in old age can improve brain plasticity above and beyond preservation of function. Existing data suggest that exercise trials aiming for improvement and preservation may require different outcome measures and that the balance between the two may depend on exercise intensity and duration, the presence of preclinical Alzheimer's disease pathology, vascular and metabolic risk factors and genetic variability.},
  language  = {en}
}
@article{SendtnerCarrollHoltmannetal.1994,
  author    = {Sendtner, Michael and Carroll, P. and Holtmann, B and Hughes, R. A. and Thoenen, H.},
  title     = {Ciliary Neurotrophic Factor},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-42545},
  year      = {1994},
  abstract  = {No abstract available},
  language  = {en}
}
@article{SendtnerKreutzbergThoenen1990,
  author    = {Sendtner, Michael and Kreutzberg, Georg W. and Thoenen, Hans},
  title     = {Ciliary neurotrophic factor (CNTF) prevents the degeneration of motor neurons after axotomy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32637},
  year      = {1990},
  abstract  = {The period of natural cell death in the development of rodent motor neurons is followed by a period of sensitivity to axonal injury1-3. In the rat this early postnatal period of vulnerability coincides with that of very low ciliary neurotrophic factor (CNTF) levels in the sciatic nerve before CNTF increases to the high, adult levels4. The developmental time course of CNTF expression, its regional tissue distribution and its cytosolic localization (as suggested by its primary structure)4*5 favour a role for CNTF as a lesion factor rather than a target-derived neurotrophic molecule like nerve growth factor. Nevertheless CNTF exhibits neurotrophic activity in vitro on different populations of embryonic neurons6. To determine whether the vulnerability of motor neurons to axotomy in the early postnatal phase is due to insufficient availability of CNTF, we transected the axons of newborn rat motor neurons and demonstrated that iocal application of CNTF prevents the degeneration of the corresponding cell bodies.},
  language  = {en}
}
@article{SaadatSendtnerRohrer1989,
  author    = {Saadat, S. and Sendtner, Michael and Rohrer, H.},
  title     = {Ciliary neurotrophic factor induces cholinergic differentiation of rat sympathetic neurons in culture},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32677},
  year      = {1989},
  abstract  = {Ciliary neurotrophic factor (CNTF) influences the levels of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in cultures of dissociated sYmpathetic neurons from newborn rats. In the presence of CNTF both the total and specific activity of ChAT was increased 7 d after culture by 15- and 18-fold, respectively, as compared to cultures kept in the absence of CNTF. Between 3 and 21 d in culture in the presence of CNTF . the total ChAT activity increased by a factor of >100. Immunotitration demonstrated that the elevated ChAT levels were due to an increased number of enzyme molecules. In contrast to the increase in ChAT levels, the total and specific activity levels' of TH were decreased by 42 and 36 \%, respectively, after 7 d in culture. Half-maximal effects for both ChAT increase and TH decrease were obtained at CNTF concentrations of rvO.6 ng and maximal levels were reached at I ng of CNTF per milliliter of medium. The effect of CNTF on TH and ChAT levels were seen in serum-containing medium as well as in serum-free medium. CNTF was shown to have only a small effect on the long-term s.urviVal of rat sympathetic neurons. We therefore concluded that the effects of CNTF on ChAT and TH are not due to selective survival of cells that acquire cholinergic traits in vitro, but are rather due to the induction of cholinergic differentiation of noradrenergic sympathetic neurons.},
  language  = {en}
}