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Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse
Journal article   Open access   Peer reviewed

Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse

Gregory E. Bigford, Valerie C. Bracchi-Ricard, Robert W. Keane, Mark S. Nash and John R Bethea
ASN neuro, v 5(4), pp 243-255
04 Sep 2013
DOI: https://doi.org/10.1042/AN20130021
PMID: 23924318
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1042/an20130021View
Published, Version of Record (VoR)CC BY-NC V4.0,  Open
url
https://doi.org/10.1042/AN20130021View
Published, Version of Record (VoR) Open

Abstract

ARC, arcuate nucleus ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD, q.v.) CNS, central nervous system CVD, cardiovascular disease DAMPS, damage–associated molecular pattern molecules FAO, fatty acid oxidation HRP, horseradish peroxidase IACUC, Institutional Animal Care and Use Committee IL, interleukin JAK, Janus kinase MYPT1, myosin phosphatase target subunit 1 neuroendocrine NLRP3, NOD-like receptor family, pyrin domain containing 3 NPY, neuropeptide Y PFA, paraformaldehyde POMC, proopiomelanocortin PVN, paraventricular nucleus RBD, Rho-binding domain ROCK, Rho-associated kinase S11 SCI, spinal cord injury STAT, signal transducer and activator of transcription VAT, visceral adipose tissue Cardiovascular Disease Metabolism Pathophysiology Signal Transduction Spinal Cord Injury
CVD (cardiovascular disease) represents a leading cause of mortality in chronic SCI (spinal cord injury). Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin) and increased NPY (neuropeptide-Y) expression in the hypothalamic ARC (arcuate nucleus) and PVN (paraventricular nucleus), 1-month post-SCI. Long-form leptin receptor (Ob-Rb), JAK2 (Janus kinase)/STAT3 (signal transducer and activator of transcription 3)/p38 and RhoA/ROCK (Rho-associated kinase) signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome in VAT (visceral adipose tissue) and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#2 Zero Hunger
#3 Good Health and Well-Being

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Web of Science research areas
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