Neuronal production of lipocalin-2 as a help-me signal for glial activation
| Autor: | Emiri T. Mandeville, Chongjie Cheng, Josephine Lok, Wendy Leung, Eng H. Lo, Joan Montaner, Klaus van Leyen, Changhong Xing, Xiaoying Wang, Xiaoshu Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology medicine.medical_specialty Ischemia Lipocalin Signal Article Brain Ischemia Brain ischemia Lipocalin-2 Proto-Oncogene Proteins Neuroplasticity medicine Animals Humans Single-Blind Method Rats Wistar Aged Advanced and Specialized Nursing Cerebral Cortex Neurons Neuronal Plasticity integumentary system Microglia business.industry Acute-phase protein medicine.disease Lipocalins Rats Stroke medicine.anatomical_structure Phenotype nervous system Cerebral cortex Astrocytes Female Neurology (clinical) Cardiology and Cardiovascular Medicine business Neuroscience Biomarkers Acute-Phase Proteins |
| Zdroj: | Stroke. 45(7) |
| ISSN: | 1524-4628 |
| Popis: | Background and Purpose— We explored the hypothesis that injured neurons release lipocalin-2 as a help me signal. Methods— In vivo lipocalin-2 responses were assessed in rat focal cerebral ischemia and human stroke brain samples using a combination of ELISA and immunostaining. In vitro, microglia and astrocytes were exposed to lipocalin-2, and various markers and assays of glial activation were quantified. Functional relevance of neuron-to-glia lipocalin-2 signaling was examined by transferring conditioned media from lipocalin-2–activated microglia and astrocytes onto neurons to see whether activated glia could protect neurons against oxygen–glucose deprivation and promote neuroplasticity. Results— In human stroke samples and rat cerebral ischemia, neuronal expression of lipocalin-2 was significantly increased. In primary cell cultures, exposing microglia and astrocytes to lipocalin-2 resulted in glial activation. In microglia, lipocalin-2 converted resting ramified shapes into a long-rod morphology with reduced branching, increased interleukin-10 release, and enhanced phagocytosis. In astrocytes, lipocalin-2 upregulated glial fibrillary acid protein, brain-derived neurotropic factor, and thrombospondin-1. Conditioned media from lipocalin-2–treated astrocytes upregulated synaptotagmin, and conditioned media from lipocalin-2–treated microglia upregulated synaptophysin and post-synaptic density 95 (PSD95) and protected neurons against oxygen–glucose deprivation. Conclusions— These findings provide proof of concept that lipocalin-2 is released by injured neurons as a help me distress signal that activates microglia and astrocytes into potentially prorecovery phenotypes. |
| Databáze: | OpenAIRE |
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