Systemic lipopolysaccharide-mediated alteration of cortical neuromodulation involves increases in monoamine oxidase-A and acetylcholinesterase activity

Journal of Neuroinflammation

Lane K Bekar¹  Grzegorz Sawicki³  Matthew E Loewen²  John C Ching²  Robert T Appleton¹  Caitlin A Wotton¹  Zhi Ming¹ 

[1] Department of Pharmacology, University of Saskatchewan, 107 Wiggins road, Saskatoon S7N 5E5, SK, Canada;Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Drive, Saskatoon S7N 5E5, SK, Canada;Department of Clinical Chemistry, Medical University of Wroclaw, Wybrzeże L. Pasteura 1, Wroclaw 50-556, Poland

关键词: Cortical inhibition;    Cortical network;    Phasic neuromodulator release;    Inflammation;   

Others  :  1133029
DOI  :  10.1186/s12974-015-0259-y

 received in 2014-09-01, accepted in 2015-02-02,  发布年份 2015

【 摘 要 】

Background

Lipopolysaccharide (LPS)-mediated sickness behaviour is known to be a result of increased inflammatory cytokines in the brain. Inflammatory cytokines have been shown to mediate increases in brain excitation by loss of GABA_A-mediated inhibition through receptor internalization or inactivation. Inflammatory pathways, reactive oxygen species and stress are also known to increase monoamine oxidase-A (MAO-A) and acetylcholinesterase (ACh-E) activity. Given that neuromodulator actions on neural circuits largely depend on inhibitory pathways and are sensitive to alteration in corresponding catalytic enzyme activities, we assessed the impact of systemic LPS on neuromodulator-mediated shaping of a simple cortical network.

Methods

Extracellular field recordings of evoked postsynaptic potentials in adult mouse somatosensory cortical slices were used to evaluate effects of a single systemic LPS challenge on neuromodulator function 1 week later. Neuromodulators were administered transiently as a bolus (100 μl) to the bath perfusate immediately upstream of the recording site to mimic phasic release of neuromodulators and enable assessment of response temporal dynamics.

Results

Systemic LPS administration resulted in loss of both spontaneous and evoked inhibition as well as alterations in the temporal dynamics of neuromodulator effects on a paired-pulse paradigm. The effects on neuromodulator temporal dynamics were sensitive to the Monoamine oxidase-A (MAO-A) antagonist clorgyline (for norepinephrine and serotonin) and the ACh-E inhibitor donepezil (for acetylcholine). This is consistent with significant increases in total MAO and ACh-E activity found in hemi-brain samples from the LPS-treated group, supporting the notion that systemic LPS administration may lead to longer-lasting changes in inhibitory network function and enzyme (MAO/ACh-E) activity responsible for reduced neuromodulator actions.

Conclusions

Given the significant role of neuromodulators in behavioural state and cognitive processes, it is possible that an inflammatory-mediated change in neuromodulator action plays a role in LPS-induced cognitive effects and could help define the link between infection and neuropsychiatric/degenerative conditions.

【 授权许可】

   
2015 Ming et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]Burton MD, Sparkman NL, Johnson RW: Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior. J Neuroinflammation. 2011, 8:54. BioMed Central Full Text
• [2]Teeling JL, Cunningham C, Newman TA, Perry VH: The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1. Brain Behav Immun. 2010, 24:409-19.
• [3]Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW: Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun. 2008, 22:301-11.
• [4]Sparkman NL, Buchanan JB, Heyen JR, Chen J, Beverly JL, Johnson RW: Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. J Neurosci. 2006, 26:10709-16.
• [5]Bluthe RM, Walter V, Parnet P, Laye S, Lestage J, Verrier D, et al.: Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III. 1994, 317:499-503.
• [6]Bluthe RM, Laye S, Michaud B, Combe C, Dantzer R, Parnet P: Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. Eur J Neurosci. 2000, 12:4447-56.
• [7]Bluthe RM, Michaud B, Poli V, Dantzer R: Role of IL-6 in cytokine-induced sickness behavior: a study with IL-6 deficient mice. Physiol Behav. 2000, 70:367-73.
• [8]Konsman JP, Luheshi GN, Bluthé RM, Dantzer R: The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis. Eur J Neurosci. 2000, 12:4434-46.
• [9]Konsman JP, Parnet P, Dantzer R: Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci. 2002, 25:154-9.
• [10]Pan W, Kastin AJ: TNFalpha transport across the blood-brain barrier is abolished in receptor knockout mice. Exp Neurol. 2002, 174:193-200.
• [11]Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, et al.: Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007, 55:453-62.
• [12]Kelley KW, Bluthe RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, et al.: Cytokine-induced sickness behavior. Brain Behav Immun. 2003, 17(Suppl 1):S112-8.
• [13]Godbout JP, Moreau M, Lestage J, Chen J, Sparkman NL, O'Connor J, et al.: Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology. 2008, 33:2341-51.
• [14]Garcia-Oscos F, Salgado H, Hall S, Thomas F, Farmer GE, Bermeo J, et al.: The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biol Psychiatry. 2012, 71:574-82.
• [15]Beattie EC, Stellwagen D, Morishita W, Bresnahan JC, Ha BK, Von Zastrow M, et al.: Control of synaptic strength by glial TNFalpha. Science. 2002, 295:2282-5.
• [16]Stellwagen D, Malenka RC: Synaptic scaling mediated by glial TNF-alpha. Nature. 2006, 440:1054-9.
• [17]Stellwagen D, Beattie EC, Seo JY, Malenka RC: Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci. 2005, 25:3219-28.
• [18]Johnson S, Stockmeier CA, Meyer JH, Austin MC, Albert PR, Wang J, et al.: The reduction of R1, a novel repressor protein for monoamine oxidase A, in major depressive disorder. Neuropsychopharmacology. 2011, 36:2139-48.
• [19]Grunewald M, Johnson S, Lu D, Wang Z, Lomberk G, Albert PR, et al.: Mechanistic role for a novel glucocorticoid-KLF11 (TIEG2) protein pathway in stress-induced monoamine oxidase A expression. J Biol Chem. 2012, 287:24195-206.
• [20]Ou XM, Chen K, Shih JC: Glucocorticoid and androgen activation of monoamine oxidase A is regulated differently by R1 and Sp1. J Biol Chem. 2006, 281:21512-25.
• [21]Cao X, Rui L, Pennington PR, Chlan-Fourney J, Jiang Z, Wei Z, et al.: Serine 209 resides within a putative p38(MAPK) consensus motif and regulates monoamine oxidase-A activity. J Neurochem. 2009, 111:101-10.
• [22]Li Y, Liu L, Kang J, Sheng JG, Barger SW, Mrak RE, et al.: Neuronal-glial interactions mediated by interleukin-1 enhance neuronal acetylcholinesterase activity and mRNA expression. J Neurosci. 2000, 20:149-55.
• [23]Bond CE, Patel P, Crouch L, Tetlow N, Day T, Abu-Hayyeh S, et al.: Astroglia up-regulate transcription and secretion of ‘readthrough’ acetylcholinesterase following oxidative stress. Eur J Neurosci. 2006, 24:381-6.
• [24]Bond CE, Greenfield SA: Multiple cascade effects of oxidative stress on astroglia. Glia. 2007, 55:1348-61.
• [25]Kirkwood A, Rozas C, Kirkwood J, Perez F, Bear MF: Modulation of long-term synaptic depression in visual cortex by acetylcholine and norepinephrine. J Neurosci. 1999, 19:1599-609.
• [26]Seol GH, Ziburkus J, Huang S, Song L, Kim IT, Takamiya K, et al.: Neuromodulators control the polarity of spike-timing-dependent synaptic plasticity. Neuron. 2007, 55:919-29.
• [27]Can A, Dao DT, Terrillion CE, Piantadosi SC, Bhat S, Gould TD: The tail suspension test. J Vis Exp 2012.
• [28]Cryan JF, O'Leary OF, Jin SH, Friedland JC, Ouyang M, Hirsch BR, et al.: Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. Proc Natl Acad Sci U S A. 2004, 101:8186-91.
• [29]Ellman GL, Courtney KD, Andres V, Feather-Stone RM: A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961, 7:88-95.
• [30]Ljubisavljevic S, Stojanovic I. Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection. Rev Neurosci. 2014. doi:10.1515/revneuro-2014-0060.
• [31]Ljubisavljevic S, Stojanovic I, Pavlovic R, Pavlovic D: The importance of nitric oxide and arginase in the pathogenesis of acute neuroinflammation: are those contra players with the same direction? Neurotox Res. 2014, 26:392-9.
• [32]Salgado H, Bellay T, Nichols JA, Bose M, Martinolich L, Perrotti L, et al.: Muscarinic M2 and M1 receptors reduce GABA release by Ca2+ channel modulation through activation of PI3K/Ca2+ − independent and PLC/Ca2+ − dependent PKC. J Neurophysiol. 2007, 98:952-65.
• [33]Xiao Z, Deng PY, Yang C, Lei S: Modulation of GABAergic transmission by muscarinic receptors in the entorhinal cortex of juvenile rats. J Neurophysiol. 2009, 102:659-69.
• [34]Lei S, Deng PY, Porter JE, Shin HS: Adrenergic facilitation of GABAergic transmission in rat entorhinal cortex. J Neurophysiol. 2007, 98:2868-77.
• [35]Salgado H, Garcia-Oscos F, Patel A, Martinolich L, Nichols JA, Dinh L, et al.: Layer-specific noradrenergic modulation of inhibition in cortical layer II/III. Cereb Cortex. 2011, 21:212-21.
• [36]Salgado H, Garcia-Oscos F, Martinolich L, Hall S, Restom R, Tseng KY, et al.: Pre- and postsynaptic effects of norepinephrine on γ-aminobutyric acid-mediated synaptic transmission in layer 2/3 of the rat auditory cortex. Synapse. 2012, 66:20-8.
• [37]Deng PY, Poudel SK, Rojanathammanee L, Porter JE, Lei S: Serotonin inhibits neuronal excitability by activating two-pore domain k + channels in the entorhinal cortex. Mol Pharmacol. 2007, 72:208-18.
• [38]Deng PY, Lei S: Serotonin increases GABA release in rat entorhinal cortex by inhibiting interneuron TASK-3 K+ channels. Mol Cell Neurosci. 2008, 39:273-84.