Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity

Authors: Wei-Xing Zhao, Jun-Han Zhang, Jiang-Bei Cao, Wei Wang, Dong-Xin Wang, Xiao-Ying Zhang, Jun Yu, Yong-Yi Zhang, You-Zhi Zhang, Wei-Dong Mi

Published in: Journal of Neuroinflammation | Issue 1/2017

Login to get access

Abstract

Background

Considerable evidence has shown that neuroinflammation and oxidative stress play an important role in the pathophysiology of postoperative cognitive dysfunction (POCD) and other progressive neurodegenerative disorders. Increasing evidence suggests that acetaminophen (APAP) has unappreciated antioxidant and anti-inflammatory properties. However, the impact of APAP on the cognitive sequelae of inflammatory and oxidative stress is unknown. The objective of this study is to explore whether APAP could have neuroprotective effects on lipopolysaccharide (LPS)-induced cognitive impairment in mice.

Methods

A mouse model of LPS-induced cognitive impairment was established to evaluate the neuroprotective effects of APAP against LPS-induced cognitive impairment. Adult C57BL/6 mice were treated with APAP half an hour prior to intracerebroventricular microinjection of LPS and every day thereafter, until the end of the study period. The Morris water maze was used to assess cognitive function from postinjection days 1 to 3. Animal behavioural tests as well as pathological and biochemical assays were performed to evaluate LPS-induced hippocampal damage and the neuroprotective effect of APAP.

Results

Mice treated with LPS exhibited impaired performance in the Morris water maze without changing spontaneous locomotor activity, which was ameliorated by treatment with APAP. APAP suppressed the accumulation of pro-inflammatory cytokines and microglial activation induced by LPS in the hippocampus. In addition, APAP increased SOD activity, reduced MDA levels, modulated glycogen synthase kinase 3β (GSK3β) activity and elevated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Moreover, APAP significantly decreased the Bax/Bcl-2 ratio and neuron apoptosis in the hippocampus of LPS-treated mice.

Conclusions

Our results suggest that APAP may possess a neuroprotective effect against LPS-induced cognitive impairment and inflammatory and oxidative stress via mechanisms involving its antioxidant and anti-inflammatory properties, as well as its ability to inhibit the mitochondrial permeability transition (MPT) pore and the subsequent apoptotic pathway.
Literature
1.
Shoair OA, Grasso Ii MP, Lahaye LA, Daniel R, Biddle CJ, Slattum PW. Incidence and risk factors for postoperative cognitive dysfunction in older adults undergoing major noncardiac surgery: a prospective study. J Anaesthesiol Clin Pharmacol. 2015;31:30–6.CrossRefPubMedPubMedCentral
2.
Hovens IB, Schoemaker RG, van der Zee EA, Heineman E, Izaks GJ, van Leeuwen BL. Thinking through postoperative cognitive dysfunction: how to bridge the gap between clinical and pre-clinical perspectives. Brain Behav Immun. 2012;26:1169–79.CrossRefPubMed
3.
Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998;351:857–61.CrossRefPubMed
4.
Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS, Group I. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009;110:548–55.CrossRefPubMed
5.
Gao HM, Hong JS. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008;29:357–65.CrossRefPubMedPubMedCentral
6.
Infante-Duarte C, Waiczies S, Wuerfel J, Zipp F. New developments in understanding and treating neuroinflammation. J Mol Med (Berl). 2008;86:975–85.CrossRef
7.
Skaper SD. The brain as a target for inflammatory processes and neuroprotective strategies. Ann N Y Acad Sci. 2007;1122:23–34.CrossRefPubMed
8.
Peng S, Zhao S, Yan F, Cheng J, Huang L, Chen H, Liu Q, Ji X, Yuan Z. HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death. J Neurosci. 2015;35:1250–9.CrossRefPubMed
9.
Xia SF, Xie ZX, Qiao Y, Li LR, Cheng XR, Tang X, Shi YH, Le GW. Differential effects of quercetin on hippocampus-dependent learning and memory in mice fed with different diets related with oxidative stress. Physiol Behav. 2015;138:325–31.CrossRefPubMed
10.
Wang P, Cao J, Liu N, Ma L, Zhou X, Zhang H, Wang Y. Protective effects of edaravone in adult rats with surgery and lipopolysaccharide administration-induced cognitive function impairment. PLoS One. 2016;11:e0153708.CrossRefPubMedPubMedCentral
11.
Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, Johnson RW. Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J. 2005;19:1329–31.PubMed
12.
Ullah F, Ali T, Ullah N, Kim MO. Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain. Neurochem Int. 2015;90:114–24.CrossRefPubMed
13.
Banoub JH, El Aneed A, Cohen AM, Joly N. Structural investigation of bacterial lipopolysaccharides by mass spectrometry and tandem mass spectrometry. Mass Spectrom Rev. 2010;29:606–50.PubMed
14.
Belarbi K, Jopson T, Tweedie D, Arellano C, Luo W, Greig NH, Rosi S. TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation. J Neuroinflammation. 2012;9:23.CrossRefPubMedPubMedCentral
15.
Bossu P, Cutuli D, Palladino I, Caporali P, Angelucci F, Laricchiuta D, Gelfo F, De Bartolo P, Caltagirone C, Petrosini L. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-alpha and IL-18. J Neuroinflammation. 2012;9:101.CrossRefPubMedPubMedCentral
16.
Huang HJ, Chen YH, Liang KC, Jheng YS, Jhao JJ, Su MT, Lee-Chen GJ, Hsieh-Li HM. Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection. PLoS One. 2012;7:e39656.CrossRefPubMedPubMedCentral
17.
Schnydrig S, Korner L, Landweer S, Ernst B, Walker G, Otten U, Kunz D. Peripheral lipopolysaccharide administration transiently affects expression of brain-derived neurotrophic factor, corticotropin and proopiomelanocortin in mouse brain. Neurosci Lett. 2007;429:69–73.CrossRefPubMed
18.
Semmler A, Frisch C, Debeir T, Ramanathan M, Okulla T, Klockgether T, Heneka MT. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp Neurol. 2007;204:733–40.CrossRefPubMed
19.
Zhang XY, Cao JB, Zhang LM, Li YF, Mi WD. Deferoxamine attenuates lipopolysaccharide-induced neuroinflammation and memory impairment in mice. J Neuroinflammation. 2015;12:20.CrossRefPubMedPubMedCentral
20.
Hritcu L, Ciobica A, Stefan M, Mihasan M, Palamiuc L, Nabeshima T. Spatial memory deficits and oxidative stress damage following exposure to lipopolysaccharide in a rodent model of Parkinson’s disease. Neurosci Res. 2011;71:35–43.CrossRefPubMed
21.
Maesschalck PJ. Efficacy and safety of ibuprofen and paracetamol in fever among children. J Pharm Belg. 2011;2:44–5.
22.
23.
Maharaj DS, Saravanan KS, Maharaj H, Mohanakumar KP, Daya S. Acetaminophen and aspirin inhibit superoxide anion generation and lipid peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats. Neurochem Int. 2004;44:355–60.CrossRefPubMed
24.
Maharaj H, Maharaj DS, Daya S. Acetylsalicylic acid and acetaminophen protect against oxidative neurotoxicity. Metab Brain Dis. 2006;21:189–99.CrossRefPubMed
25.
26.
27.
Naziroglu M, Uguz AC, Kocak A, Bal R. Acetaminophen at different doses protects brain microsomal Ca2+-ATPase and the antioxidant redox system in rats. J Membr Biol. 2009;231:57–64.CrossRefPubMed
28.
Locke CJ, Fox SA, Caldwell GA, Caldwell KA. Acetaminophen attenuates dopamine neuron degeneration in animal models of Parkinson’s disease. Neurosci Lett. 2008;439:129–33.CrossRefPubMed
29.
Pitchaimani V, Arumugam S, Thandavarayan RA, Thiyagarajan MK, Aiyalu R, Sreedhar R, Nakamura T, Watanabe K. Nootropic activity of acetaminophen against colchicine induced cognitive impairment in rats. J Clin Biochem Nutr. 2012;50:241–4.CrossRefPubMedPubMedCentral
30.
Chaviaras S, Mak P, Ralph D, Krishnan L, Broadbear JH. Assessing the antidepressant-like effects of carbetocin, an oxytocin agonist, using a modification of the forced swimming test. Psychopharmacology (Berl). 2010;210:35–43.CrossRef
31.
32.
Hua F, Wang J, Ishrat T, Wei W, Atif F, Sayeed I, Stein DG. Genomic profile of Toll-like receptor pathways in traumatically brain-injured mice: effect of exogenous progesterone. J Neuroinflammation. 2011;8:42.CrossRefPubMedPubMedCentral
33.
Skelly DT, Hennessy E, Dansereau MA, Cunningham C. A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1beta, [corrected] TNF-alpha and IL-6 challenges in C57BL/6 mice. PLoS One. 2013;8:e69123.CrossRefPubMedPubMedCentral
34.
Norden DM, Trojanowski PJ, Villanueva E, Navarro E, Godbout JP. Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia. 2016;64:300–16.CrossRefPubMed
35.
Lawson MA, McCusker RH, Kelley KW. Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice. J Neuroinflammation. 2013;10:54.PubMedPubMedCentral
36.
Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuna-Castroviejo D. A review of the evidence supporting melatonin’s role as an antioxidant. J Pineal Res. 1995;18:1–11.CrossRefPubMed
37.
Zhang C, Li C, Xu Z, Zhao S, Li P, Cao J, Mi W. The effect of surgical and psychological stress on learning and memory function in aged C57BL/6 mice. Neuroscience. 2016;320:210–20.CrossRefPubMed
38.
McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004;1035:104–16.CrossRefPubMed
39.
Ren L, Lubrich B, Biber K, Gebicke-Haerter PJ. Differential expression of inflammatory mediators in rat microglia cultured from different brain regions. Brain Res Mol Brain Res. 1999;65:198–205.CrossRefPubMed
40.
Raber J, Sorg O, Horn TF, Yu N, Koob GF, Campbell IL, Bloom FE. Inflammatory cytokines: putative regulators of neuronal and neuro-endocrine function. Brain Res Brain Res Rev. 1998;26:320–6.CrossRefPubMed
41.
Rosi S, Vazdarjanova A, Ramirez-Amaya V, Worley PF, Barnes CA, Wenk GL. Memantine protects against LPS-induced neuroinflammation, restores behaviorally-induced gene expression and spatial learning in the rat. Neuroscience. 2006;142:1303–15.CrossRefPubMed
42.
Zielasek J, Hartung HP. Molecular mechanisms of microglial activation. Adv Neuroimmunol. 1996;6:191–22.CrossRefPubMed
43.
44.
Jope RS, Johnson GV. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci. 2004;29:95–102.CrossRefPubMed
45.
Bath KG, Akins MR, Lee FS. BDNF control of adult SVZ neurogenesis. Dev Psychobiol. 2012;54:578–89.CrossRefPubMed
46.
Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA. Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci. 2001;21:6718–31.PubMed
47.
Wang Y, Liu X, Zhang D, Chen J, Liu S, Berk M. The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction. BMC Med. 2013;11:32.CrossRefPubMedPubMedCentral
48.
Ishida T, Sato T, Irifune M, Tanaka K, Nakamura N, Nishikawa T. Effect of acetaminophen, a cyclooxygenase inhibitor, on Morris water maze task performance in mice. J Psychopharmacol. 2007;21:757–67.CrossRefPubMed
49.
Casper D, Yaparpalvi U, Rempel N, Werner P. Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Neurosci Lett. 2000;289:201–4.CrossRefPubMed
50.
Hernandes MS, D'Avila JC, Trevelin SC, Reis PA, Kinjo ER, Lopes LR, Castro-Faria-Neto HC, Cunha FQ, Britto LR, Bozza FA. The role of Nox2-derived ROS in the development of cognitive impairment after sepsis. J Neuroinflammation. 2014;11:36.CrossRefPubMedPubMedCentral
51.
Pinheiro da Silva F, Machado MC, Velasco IT. Neuropeptides in sepsis: from brain pathology to systemic inflammation. Peptides. 2013;44:135–8.CrossRefPubMed
52.
Brandeis R, Brandys Y, Yehuda S. The use of the Morris water maze in the study of memory and learning. Int J Neurosci. 1989;48:29–69.CrossRefPubMed
53.
Dong Z, Bai Y, Wu X, Li H, Gong B, Howland JG, Huang Y, He W, Li T, Wang YT. Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology. 2013;64:65–73.CrossRefPubMed
54.
da Silva DJ, Borges AF, Souza PO, de Souza PR, Cardoso CR, Dorta ML, de Oliveira MA, Teixeira AL, Ribeiro-Dias F. Decreased Toll-like receptor 2 and Toll-like receptor 7/8-induced cytokines in Parkinson’s disease patients. Neuroimmunomodulation. 2016;23:58–66.CrossRefPubMed
55.
McGeer PL. Cyclo-oxygenase-2 inhibitors: rationale and therapeutic potential for Alzheimer’s disease. Drugs Aging. 2000;17:1–11.CrossRefPubMed
56.
McGeer PL, McGeer EG. Inflammation of the brain in Alzheimer’s disease: implications for therapy. J Leukoc Biol. 1999;65:409–15.PubMed
57.
Bisaglia M, Venezia V, Piccioli P, Stanzione S, Porcile C, Russo C, Mancini F, Milanese C, Schettini G. Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid beta-peptides induced oxidative stress and reduces NF-kappaB activation. Neurochem Int. 2002;41:43–54.CrossRefPubMed
58.
Landolfi C, Soldo L, Polenzani L, Apicella C, Capezzone de Joannon A, Coletta I, Di Cesare F, Brufani M, Pinza M, Milanese C. Inflammatory molecule release by beta-amyloid-treated T98G astrocytoma cells: role of prostaglandins and modulation by paracetamol. Eur J Pharmacol. 1998;360:55–64.CrossRefPubMed
59.
Yatin SM, Varadarajan S, Butterfield DA. Vitamin E prevents Alzheimer’s amyloid beta-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production. J Alzheimers Dis. 2000;2:123–31.PubMed
60.
Khan MS, Ali T, Kim MW, Jo MH, Jo MG, Badshah H, Kim MO. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Neurochem Int. 2016;100:1–10.CrossRefPubMed
61.
Rimessi A, Previati M, Nigro F, Wieckowski MR, Pinton P. Mitochondrial reactive oxygen species and inflammation: molecular mechanisms, diseases and promising therapies. Int J Biochem Cell Biol. 2016;81:281–93.CrossRefPubMed
62.
Ozmen I, Naziroglu M, Alici HA, Sahin F, Cengiz M, Eren I. Spinal morphine administration reduces the fatty acid contents in spinal cord and brain by increasing oxidative stress. Neurochem Res. 2007;32:19–25.CrossRefPubMed
63.
Eren I, Naziroglu M, Demirdas A. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res. 2007;32:1188–95.CrossRefPubMed
64.
Jope RS, Yuskaitis CJ, Beurel E. Glycogen synthase kinase-3 (GSK3): inflammation, diseases, and therapeutics. Neurochem Res. 2007;32:577–95.CrossRefPubMed
65.
Martin M, Rehani K, Jope RS, Michalek SM. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 2005;6:777–84.CrossRefPubMedPubMedCentral
66.
Llorens-Martin M, Fuster-Matanzo A, Teixeira CM, Jurado-Arjona J, Ulloa F, Defelipe J, Rabano A, Hernandez F, Soriano E, Avila J. GSK-3beta overexpression causes reversible alterations on postsynaptic densities and dendritic morphology of hippocampal granule neurons in vivo. Mol Psychiatry. 2013;18:451–60.CrossRefPubMed
67.
Frame S, Cohen P, Biondi RM. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol Cell. 2001;7:1321–7.CrossRefPubMed
68.
He Y, Zhou A, Jiang W. Toll-like receptor 4-mediated signaling participates in apoptosis of hippocampal neurons. Neural Regen Res. 2013;8:2744–53.PubMedPubMedCentral
69.
Grimes CA, Jope RS. The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. Prog Neurobiol. 2001;65:391–426.CrossRefPubMed
70.
Maharaj H, Maharaj DS, Daya S. Acetylsalicylic acid and acetaminophen protect against MPP+-induced mitochondrial damage and superoxide anion generation. Life Sci. 2006;78:2438–43.CrossRefPubMed
71.
Leal G, Afonso PM, Salazar IL, Duarte CB. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res. 2015;1621:82–101.CrossRefPubMed
72.
Guan Z, Fang J. Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats. Brain Behav Immun. 2006;20:64–71.CrossRefPubMed
73.
Ma L, Zhang H, Liu N, Wang PQ, Guo WZ, Fu Q, Jiao LB, Ma YQ, Mi WD. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration. Brain Res Bull. 2016;121:192–200.CrossRefPubMed
74.
Wu CW, Chen YC, Yu L, Chen HI, Jen CJ, Huang AM, Tsai HJ, Chang YT, Kuo YM. Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. J Neurochem. 2007;103:2471–81.CrossRefPubMed
75.
Scott Bitner R. Cyclic AMP response element-binding protein (CREB) phosphorylation: a mechanistic marker in the development of memory enhancing Alzheimer’s disease therapeutics. Biochem Pharmacol. 2012;83:705–14.CrossRefPubMed
76.
Wang G, Wang W, Zhao J, Ni Y, Zhou X, Zhang W. Ghrelin prevents neuronal apoptosis and cognitive impairments in sepsis-associated encephalopathy. Neuroreport. 2011;22:959–64.CrossRefPubMed
77.
Zhou TF, Yu JG. Recombinant human erythropoietin attenuates neuronal apoptosis and cognitive defects via JAK2/STAT3 signaling in experimental endotoxemia. J Surg Res. 2013;183:304–12.CrossRefPubMed
78.
Ghate NB, Das A, Chaudhuri D, Panja S, Mandal N. Sundew plant, a potential source of anti-inflammatory agents, selectively induces G2/M arrest and apoptosis in MCF-7 cells through upregulation of p53 and Bax/Bcl-2 ratio. Cell Death Discov. 2016;2:15062.CrossRefPubMedPubMedCentral
79.
Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993;75:241–51.CrossRefPubMed
80.
81.
82.
Zhang H, Li Q, Li Z, Mei Y, Guo Y. The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by analogous ischemia/reperfusion in vitro. Neurosci Res. 2008;62:140–6.CrossRefPubMed
83.
Baliga SS, Jaques-Robinson KM, Hadzimichalis NM, Golfetti R, Merrill GF. Acetaminophen reduces mitochondrial dysfunction during early cerebral postischemic reperfusion in rats. Brain Res. 2010;1319:142–54.CrossRefPubMed
84.
Rohn TT, Vyas V, Hernandez-Estrada T, Nichol KE, Christie LA, Head E. Lack of pathology in a triple transgenic mouse model of Alzheimer’s disease after overexpression of the anti-apoptotic protein Bcl-2. J Neurosci. 2008;28:3051–9.CrossRefPubMed
85.
Ghanem CI, Perez MJ, Manautou JE, Mottino AD. Acetaminophen from liver to brain: new insights into drug pharmacological action and toxicity. Pharmacol Res. 2016;109:119–31.CrossRefPubMed
Metadata
Title
Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity
Authors
Wei-Xing Zhao
Jun-Han Zhang
Jiang-Bei Cao
Wei Wang
Dong-Xin Wang
Xiao-Ying Zhang
Jun Yu
Yong-Yi Zhang
You-Zhi Zhang
Wei-Dong Mi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-016-0781-6

Other articles of this Issue 1/2017

Journal of Neuroinflammation 1/2017 Go to the issue

Review

Macrophage and nerve interaction in endometriosis

Research

Lentivirus-mediated interleukin-1β (IL-1β) knock-down in the hippocampus alleviates lipopolysaccharide (LPS)-induced memory deficits and anxiety- and depression-like behaviors in mice

Research

Purinergic receptors P2Y12R and P2X7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis

Research

Sensitization of ASIC3 by proteinase-activated receptor 2 signaling contributes to acidosis-induced nociception

Research

NOX2 deficiency alters macrophage phenotype through an IL-10/STAT3 dependent mechanism: implications for traumatic brain injury

Research

The Alzheimer’s disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway