Experimental brain research, 2019-12, Vol.237 (12), p.3351-3362
2019
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- Autor(en) / Beteiligte
- Titel
- NRG1–ErbB4 signaling promotes functional recovery in a murine model of traumatic brain injury via regulation of GABA release
- Ist Teil von
- Experimental brain research, 2019-12, Vol.237 (12), p.3351-3362
- Ort / Verlag
- Berlin/Heidelberg: Springer Berlin Heidelberg
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Traumatic brain injury (TBI) is a serious health problem in the world. However, little is known about the pathogenesis and molecular mechanisms of TBI. Here, we show that TBI activates neuregulin 1 (NRG1)-ErbB4 signaling, with an increased expression of NRG1 and ErbB4 in the traumatic region. Specifically knocking out ErbB4 in parvalbumin-positive (PV + ) interneurons exacerbates motor function deficits in mice after TBI. Consistently, PV-ErbB4 −/− mice showed larger necrotic area and more edema when compared with PV-ErbB4 +/+ mice. Replenishment of NRG1 through intranasal application of the recombinant protein in PV-ErbB4 +/+ mice enhanced neurological function. Moreover, using an in vitro neuronal culture system, we found that NRG1–ErbB4 signaling protects neurons from glutamate-induced death, and such protective effects could be diminished by GABA receptor antagonist. These results indicate that NRG-ErbB4 signaling protects cortical neurons from TBI-induced damage, and such effect is probably mediated by promoting GABA activity. Taken together, these findings unveil a previously unappreciated role for NRG1-ErB4 signaling in preventing neuronal cell death during functional recovery after TBI.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-4819eISSN: 1432-1106DOI: 10.1007/s00221-019-05680-2Titel-ID: cdi_proquest_miscellaneous_2314254036
- Format
- –
- Schlagworte
- Animal models, Animals, Behavior, Animal - physiology, Biomedical and Life Sciences, Biomedicine, Brain, Brain Injuries, Traumatic - metabolism, Brain Injuries, Traumatic - pathology, Brain Injuries, Traumatic - physiopathology, Cell culture, Cell death, Cell Death - physiology, Cells, Cultured, Disease Models, Animal, Edema, ErbB-2 protein, GABA, GABA Antagonists - pharmacology, gamma-Aminobutyric Acid - metabolism, Glutamate, Glutamic Acid - metabolism, Injuries, Interneurons, Mice, Mice, Inbred C57BL, Mice, Knockout, Molecular modelling, Neuregulin, Neuregulin 1, Neuregulin-1 - metabolism, Neuregulin-1 - pharmacology, Neurology, Neurons, Neurons - metabolism, Neuroprotection - physiology, Neurosciences, Neurotransmitters, Parietal Lobe - injuries, Parietal Lobe - metabolism, Parietal Lobe - pathology, Parietal Lobe - physiopathology, Parvalbumin, Receptor, ErbB-4 - deficiency, Receptor, ErbB-4 - metabolism, Recombinant proteins, Recovery (Medical), Recovery of function, Recovery of Function - physiology, Research Article, Signal Transduction - physiology, Traumatic brain injury, γ-Aminobutyric acid