@article{JuergensBieniussaVoelkeretal.2020,
  author    = {Juergens, Lukas and Bieniussa, Linda and Voelker, Johannes and Hagen, Rudolf and Rak, Kristen},
  title     = {Spatio-temporal distribution of tubulin-binding cofactors and posttranslational modifications of tubulin in the cochlea of mice},
  series = {Histochemistry and Cell Biology},
  volume    = {154},
  journal   = {Histochemistry and Cell Biology},
  issn      = {0948-6143},
  doi       = {10.1007/s00418-020-01905-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234852},
  pages     = {671-681},
  year      = {2020},
  abstract  = {The five tubulin-binding cofactors (TBC) are involved in tubulin synthesis and the formation of microtubules. Their importance is highlighted by various diseases and syndromes caused by dysfunction or mutation of these proteins. Posttranslational modifications (PTMs) of tubulin promote different characteristics, including stability-creating subpopulations of tubulin. Cell- and time-specific distribution of PTMs has only been investigated in the organ of Corti in gerbils. The aim of the presented study was to investigate the cell type-specific and time-specific expression patterns of TBC proteins and PTMs for the first time in murine cochleae over several developmental stages. For this, murine cochleae were investigated at the postnatal (P) age P1, P7 and P14 by immunofluorescence analysis. The investigations revealed several profound interspecies differences in the distribution of PTMs between gerbil and mouse. Furthermore, this is the first study to describe the spatio-temporal distribution of TBCs in any tissue ever showing a volatile pattern of expression. The expression analysis of TBC proteins and PTMs of tubulin reveals that these proteins play a role in the physiological development of the cochlea and might be essential for hearing.},
  language  = {en}
}
@article{EngertSpahnBieniussaetal.2023,
  author    = {Engert, Jonas and Spahn, Bjoern and Bieniussa, Linda and Hagen, Rudolf and Rak, Kristen and Voelker, Johannes},
  title     = {Neurogenic stem cell niche in the auditory Thalamus: in vitro evidence of neural stem cells in the rat medial geniculate body},
  series = {Life},
  volume    = {13},
  journal   = {Life},
  number    = {5},
  issn      = {2075-1729},
  doi       = {10.3390/life13051188},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319387},
  year      = {2023},
  abstract  = {The medial geniculate body (MGB) is a nucleus of the diencephalon representing a relevant segment of the auditory pathway and is part of the metathalamus. It receives afferent information via the inferior brachium of the inferior colliculus and transmits efferent fibers via acoustic radiations to the auditory cortex. Neural stem cells (NSCs) have been detected in certain areas along the auditory pathway. They are of great importance as the induction of an adult stem cell niche might open a regenerative approach to a causal treatment of hearing disorders. Up to now, the existence of NSCs in the MGB has not been determined. Therefore, this study investigated whether the MGB has a neural stem cell potential. For this purpose, cells were extracted from the MGB of PND 8 Sprague-Dawley rats and cultured in a free-floating cell culture assay, which showed mitotic activity and positive staining for stem cell and progenitor markers. In differentiation assays, the markers β-III-tubulin, GFAP, and MBP demonstrated the capacity of single cells to differentiate into neuronal and glial cells. In conclusion, cells from the MGB exhibited the cardinal features of NSCs: self-renewal, the formation of progenitor cells, and differentiation into all neuronal lineage cells. These findings may contribute to a better understanding of the development of the auditory pathway.},
  language  = {en}
}
@article{BieniussaKahramanSkornickaetal.2022,
  author    = {Bieniussa, Linda and Kahraman, Baran and Skornicka, Johannes and Schulte, Annemarie and Voelker, Johannes and Jablonka, Sibylle and Hagen, Rudolf and Rak, Kristen},
  title     = {Pegylated insulin-like growth factor 1 attenuates hair cell loss and promotes presynaptic maintenance of medial olivocochlear cholinergic fibers in the cochlea of the progressive motor neuropathy mouse},
  series = {Frontiers in Neurology},
  volume    = {13},
  journal   = {Frontiers in Neurology},
  issn      = {1664-2295},
  doi       = {10.3389/fneur.2022.885026},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276669},
  year      = {2022},
  abstract  = {The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of "efferent auditory neuropathy." Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.},
  language  = {en}
}