RGD Reference Report - Neuronal production of lipocalin-2 as a help-me signal for glial activation. - Rat Genome Database

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Neuronal production of lipocalin-2 as a help-me signal for glial activation.

Authors: Xing, Changhong  Wang, Xiaoshu  Cheng, Chongjie  Montaner, Joan  Mandeville, Emiri  Leung, Wendy  van Leyen, Klaus  Lok, Josephine  Wang, Xiaoying  Lo, Eng H 
Citation: Xing C, etal., Stroke. 2014 Jul;45(7):2085-92. doi: 10.1161/STROKEAHA.114.005733. Epub 2014 Jun 10.
RGD ID: 126790489
Pubmed: (View Article at PubMed) PMID:24916903
DOI: Full-text: DOI:10.1161/STROKEAHA.114.005733

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.

Disease Annotations    
Stroke  (IEP,ISO)
transient cerebral ischemia  (IEP,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component
cytoplasm  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)

Genes (Mus musculus)
Lcn2  (lipocalin 2)

Genes (Homo sapiens)
LCN2  (lipocalin 2)

Additional Information