气候变化领域集成服务门户(CCPortal): Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids

CCPortal

DOI	10.1186/s12974-020-01971-6
	Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids
	Hermes D.J.; Jacobs I.R.; Key M.C.; League A.F.; Yadav-Samudrala B.J.; Xu C.; McLane V.D.; Nass S.R.; Jiang W.; Meeker R.B.; Ignatowska-Jankowska B.M.; Lichtman A.H.; Li Z.; Wu Z.; Yuan H.; Knapp P.E.; Hauser K.F.; Fitting S.
发表日期	2020
ISSN	17422094
卷号	17 期号:1
英文摘要	Background: Human immunodeficiency virus type-1 (HIV-1) and opiates cause long-term inflammatory insult to the central nervous system (CNS) and worsen disease progression and HIV-1-related neuropathology. The combination of these proinflammatory factors reflects a devastating problem as opioids have high abuse liability and continue to be prescribed for certain patients experiencing HIV-1-related pain. Methods: Here, we examined the impact of chronic (3-month) HIV-1 transactivator of transcription (Tat) exposure to short-term (8-day), escalating morphine in HIV-1 Tat transgenic mice that express the HIV-1 Tat protein in a GFAP promoter-regulated, doxycycline (DOX)-inducible manner. In addition to assessing morphine-induced tolerance in nociceptive responses organized at spinal (i.e., tail-flick) and supraspinal (i.e., hot-plate) levels, we evaluated neuroinflammation via positron emission tomography (PET) imaging using the [18F]-PBR111 ligand, immunohistochemistry, and cytokine analyses. Further, we examined endocannabinoid (eCB) levels, related non-eCB lipids, and amino acids via mass spectrometry. Results: Tat-expressing [Tat(+)] transgenic mice displayed antinociceptive tolerance in the tail withdrawal and hot-plate assays compared to control mice lacking Tat [Tat(−)]. This tolerance was accompanied by morphine-dependent increases in Iba-1 ± 3-nitrotryosine immunoreactive microglia, and alterations in pro- and anti-inflammatory cytokines, and chemokines in the spinal cord and striatum, while increases in neuroinflammation were absent by PET imaging of [18F]-PBR111 uptake. Tat and morphine exposure differentially affected eCB levels, non-eCB lipids, and specific amino acids in a region-dependent manner. In the striatum, non-eCB lipids were significantly increased by short-term, escalating morphine exposure, including peroxisome proliferator activator receptor alpha (PPAR-α) ligands N-oleoyl ethanolamide (OEA) and N-palmitoyl ethanolamide (PEA), as well as the amino acids phenylalanine and proline. In the spinal cord, Tat exposure increased amino acids leucine and valine, while morphine decreased levels of tyrosine and valine but did not affect eCBs or non-eCB lipids. Conclusion: Overall results demonstrate that 3 months of Tat exposure increased morphine tolerance and potentially innate immune tolerance evidenced by reductions in specific cytokines (e.g., IL-1α, IL-12p40) and microglial reactivity. In contrast, short-term, escalating morphine exposure acted as a secondary stressor revealing an allostatic shift in CNS baseline inflammatory responsiveness from sustained Tat exposure. © 2020, The Author(s).
英文关键词	Aliphatic side-chain amino acids; Anti-inflammation; Chemokines; Cytokines; Endocannabinoids; Microgliosis; Opioid drug abuse; Peroxisome proliferator activator receptor α (PPAR-α) agonists; Phenylalanine; Proinflammation; [18F]-PBR111 PET imaging
scopus关键词	3 nitrotyrosine; amino acid derivative; chemokine; cytokine; doxycycline; endocannabinoid; fluorine 18; glial fibrillary acidic protein; interleukin 12p40; interleukin 1alpha; leucine; ligand; lipid; morphine sulfate; n oleoylethanolamine; opiate; palmidrol; peroxisome proliferator activated receptor alpha; peroxisome proliferator activated receptor alpha agonist; phenylalanine; proline; Tat protein; valine; allostasis; animal cell; animal experiment; animal model; animal tissue; Article; controlled study; corpus striatum; drug dose escalation; drug exposure; drug tolerance; drug uptake; hot plate test; Human immunodeficiency virus 1; immunohistochemistry; immunological tolerance; immunoreactivity; innate immunity; male; mass spectrometry; microglia; morphine-induced antinociception; mouse; nervous system inflammation; neuroprotection; nociception; nonhuman; opiate addiction; promoter region; protein analysis; protein expression; regulatory mechanism; signal transduction; spinal cord; tail flick test; transgenic mouse
来源期刊	Journal of Neuroinflammation
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/176741
作者单位	Department of Psychology & Neuroscience, University of North Carolina, Chapel Hill, NC, United States; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United States; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States; Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States; Department of Neurology, University of North Carolina, Chapel Hill, NC, United States; Okinawa Institute of Science and Technology, Neuronal Rhythms in Movement Unit, Okinawa, 904-0495, Japan; Department of Radiology, School of Medicine, University of North Carolina, Chapel Hill, NC, United States; Department of Anatomy & Neurobiology, Virginia Commonwealth University, Richmond, VA, United States
推荐引用方式 GB/T 7714	Hermes D.J.,Jacobs I.R.,Key M.C.,et al. Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids[J],2020,17(1).
APA	Hermes D.J..,Jacobs I.R..,Key M.C..,League A.F..,Yadav-Samudrala B.J..,...&Fitting S..(2020).Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids.Journal of Neuroinflammation,17(1).
MLA	Hermes D.J.,et al."Escalating morphine dosing in HIV-1 Tat transgenic mice with sustained Tat exposure reveals an allostatic shift in neuroinflammatory regulation accompanied by increased neuroprotective non-endocannabinoid lipid signaling molecules and amino acids".Journal of Neuroinflammation 17.1(2020).