Adipocyte‐derived angiopoietin‐1 supports neurite outgrowth and synaptogenesis of sensory neurons

Journal of Neuroscience Research - Tập 83 Số 7 - Trang 1160-1169 - 2006
Joanna Kosacka1, Marcin Nowicki1, Johannes Kacza2, Jürgen Borlak3, Jürgen Engele1,4, Katharina Spanel‐Borowski1,4
1Institute of Anatomy, University of Leipzig, Leipzig, Germany
2Institute of Veterinary Anatomy, University of Leipzig, Leipzig, Germany
3Fraunhofer Institute of Toxicology and Experimental Medicine, Center for Drug Research and Medical Biotechnology, Hannover, Germany
4Katharina Spanel-Borowski and Jürgen Engele contributed equally to this work.

Tóm tắt

AbstractSensory and sympathetic innervation of the white fat tissue (WAT) contributes to lipolysis. In addition, both fiber types adapt in density to weight gain and loss. Because these findings are indicative for a tight control of nerve fiber plasticity by adipokines, we tested whether adipocytes control neurite growth of sensory neurons through angiopoietin‐1 (Ang‐1). We further considered initial hints that Ang‐1‐induced neuritogenesis involves transactivation of the high‐affinity nerve growth factor (NGF) receptor trkA. Coculturing dorsal root ganglion (DRG) cells with 3T3‐L1 adipocytes supported neurite outgrowth. These neurotrophic effects were associated with the increased expression of Ang‐1 (presumably in adipocytes) as well as of trkA. The effects were abolished upon inactivating Ang‐1 in culture with selective antibodies. Likewise, neurite outgrowth was impaired in the presence of inactivating NGF antibodies as well as upon inhibition of the NGF high‐affinity trkA receptor with the antagonist K252a, indicating a tight cooperation of Ang‐1 and NGF in the control of neuritogenesis. DRG‐adipipocyte cocultures were further used to establish whether sensory neurons would form synaptic contacts with adipocytes. Electron microscopy demonstrated that cultured sensory neurons develop predominantly neuroneuronal synapses but seem to affect adipocytes by synapses en passant. Comparably to the case for neuritogenesis, expression of the presynaptic protein synaptophysin as well of the postsynaptic protein PSD‐95 correlated with Ang‐1 levels in culture. It is concluded that adipocyte‐secreted Ang‐1 supports neurite outgrowth, which is involved in synaptogenesis. The novel function of Ang‐1 appears to play a physiological role in WAT plasticity. © 2006 Wiley‐Liss, Inc.

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Journal of Neuroscience Research

Tập 83 Số 7

1160-1169

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