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Journal article
Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling
Brain, behavior, and immunity, v 41(1), pp 65-81
Oct 2014
PMCID: PMC4167189
PMID: 24938671
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Patients suffering from neuropathic pain have a higher incidence of mood disorders such as depression. Increased expression of tumor necrosis factor (TNF) has been reported in neuropathic pain and depressive-like conditions and most of the pro-inflammatory effects of TNF are mediated by the TNF receptor 1 (TNFR1). Here we sought to investigate: (1) the occurrence of depressive-like behavior in chronic neuropathic pain and the associated forms of hippocampal plasticity, and (2) the involvement of TNFR1-mediated TNF signaling as a possible regulator of such events. Neuropathic pain was induced by chronic constriction injury of the sciatic nerve in wild-type and TNFR1−/− mice. Anhedonia, weight loss and physical state were measured as symptoms of depression. Hippocampal neurogenesis, neuroplasticity, myelin remodeling and TNF/TNFRs expression were analyzed by immunohistochemical analysis and western blot assay.
We found that neuropathic pain resulted in the development of depressive symptoms in a time dependent manner and was associated with profound hippocampal alterations such as impaired neurogenesis, reduced expression of neuroplasticity markers and myelin proteins. The onset of depressive-like behavior also coincided with increased hippocampal levels of TNF, and decreased expression of TNF receptor 2 (TNFR2), which were all fully restored after mice spontaneously recovered from pain. Notably, TNFR1−/− mice did not develop depressive-like symptoms after injury, nor were there changes in hippocampal neurogenesis and plasticity.
Our data show that neuropathic pain induces a cluster of depressive-like symptoms and profound hippocampal plasticity that are dependent on TNF signaling through TNFR1.
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Details
- Title
- Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling
- Creators
- Anna Dellarole - Miami Project to Cure ParalysisPaul Morton - Miami Project to Cure ParalysisRoberta Brambilla - Miami Project to Cure ParalysisWinston Walters - Miami Project to Cure ParalysisSpencer Summers - Miami Project to Cure ParalysisDanielle Bernardes - University of MiamiMariagrazia Grilli - University of Eastern Piedmont Amadeo AvogadroJohn R. Bethea - Drexel University
- Publication Details
- Brain, behavior, and immunity, v 41(1), pp 65-81
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000341905400009
- Scopus ID
- 2-s2.0-84924076588
- Other Identifier
- 991019169573204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Neurosciences
- Psychiatry