The nervous system is an intricate network of neurons and glia cells. The goal of our research is to investigate molecular mechanisms that regulate neuron-glia interactions and orchestrate the development and adult functions of neural networks in the peripheral and central nervous system. Furthermore, we aim at a better understanding of pathological processes that compromise cellular communication and thereby promote the pathogenesis of neurological disorders, such as multiple sclerosis and schizophrenia.
We interrogate these processes by applying state-of-the-art molecular, biochemical, and histological approaches in genetically modified mice that permit spatially and temporally controlled genetic interventions. Our research is focused on a family of neural growth factors, the neuregulins (NRG), and their tyrosine kinase receptors from the ErbB family. These proteins are important regulators of neural migration, axonal pathfinding and myelination during development. In addition, NRG/ErbB signaling has been implicated in the modulation of synaptic functions and neuronal excitability in glutamatergic and GABAergic networks, and thereby may contribute to plasticity processes linked to learning and memory in the adult brain.
Selected Publications
ORCID-ID: 0000-0003-2477-2892
Hernández S., Salvany S., Casanovas A., Piedrafita L., Soto-Bernardini M.C., Tarabal O., Blasco A., Gras S., Gatius A., Schwab M.H.*, Calderó J., Esquerda J.E. (2023). Persistent NRG1 type III overexpression in spinal motor neurons has no therapeutic effect on ALS-related pathology in SODG93A mice. Neurotherapeutics. 20, 1820-1834. *senior co-author
Götze T., Soto Bernardini M.C., Zhang M., Mießner H., Brzózka M.M., Velanac V., Dullin C., Ramos-Gomes F., Peng M., Husseini H., Schifferdecke E., Alves F., Rossner M.J., Nave K.A., Zhang W., Schwab M.H. (2021). Hyperactivity is a core endophenotype of elevated juxtacrine Neuregulin-1 signaling in embryonic glutamatergic networks.
Schizophr. Bull. 47, 1409-1420.
Fledrich R., Akkermann D., Abdelaal T.A., Schuetza V., Hermes D., Schäffner E., Soto-Bernadini M.C., Götze T., Klink A., Kusch K., Krüger M., Moebius W., Brück W., Mueller W.C., Sereda M.W., Schwab M.H.*, Nave K.A., Stassart R.M. (2019). A Neuregulin-1 type I signaling axis mediates Schwann cell interactions upstream of disease hallmarks in the most common inherited demyelinating neuropathy. Nature Commun. 10,1467.
*joint corresponding author
Salvany S., Casanovas A., Tarabal O., Piedrafita L., Hernández S., Santafé M., Soto-Bernardini M.C., Calderó J., Schwab M.H.*, Esquerda J.E. (2019). Localization and dynamic changes of neuregulin-1 at C-type synaptic boutons in association with motor neuron injury and repair. FASEB J. 33, 7833-7851. *joint corresponding author
Wehr M.C., Hinrichs W., Brzózka M.M., Unterbarnscheidt T., Herholt A., Wintgens J.P., Soto-Bernardini M.C., Kravchenko M., Nave K.A., Wichert S.P., Falkai P., Zhang W., Schwab M.H., Rossner M.J. (2017). Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia-relevant endophenotypes in mice. EMBO Mol Med. 9, 1448-1462.
Lee Y., Li Y., Mikesh M., Smith I., Nave K.A., Schwab M.H., Thompson W.J. (2016). Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions. Proc Natl Acad Sci. 113, E479-87.
Agarwal A., Zhang M., Trembak-Duff I., Unterbarnscheidt T., Radyushkin K., Dibaj P., Martins de Souza D., Boretius S., Brzózka M.M., Steffens H., Berning S., Teng Z., Gummert M., Tantra M., Guest P.C., Willig K.I., Frahm J., Hell S.W., Bahn S., Rossner M.J., Nave K.A., Ehrenreich H., Zhang W., Schwab M.H. (2014). Dysregulated expression of neuregulin-1 by cortical pyramidal neurons disrupts synaptic plasticity. Cell Rep. 8,1130-1145.
Team
- Hadiseh Hosseinnia (PhD Student)
- Maria Lehning (Post Doc)
