Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs.
Animals
Anti-Anxiety Agents
/ pharmacology
Antidepressive Agents
/ pharmacology
Astrocytes
/ drug effects
Benzodiazepines
/ pharmacology
Connexin 43
/ antagonists & inhibitors
Diazepam
/ pharmacology
Fluoxetine
/ pharmacology
Male
Mice
Mice, Inbred C57BL
Selective Serotonin Reuptake Inhibitors
/ pharmacology
Connexin 43
antidepressant
anxiolytic
astrocytes
hippocampus
serotonin
Journal
Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
01
10
2019
revised:
18
12
2019
accepted:
02
01
2020
pubmed:
12
1
2020
medline:
22
7
2021
entrez:
12
1
2020
Statut:
ppublish
Résumé
Astroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available psychotropic drugs is still unknown. To investigate this, we evaluated the behavioural effects of the genetic and pharmacological inactivation of Cx43 on the antidepressant- and anxiolytic-like activities of the selective serotonin reuptake inhibitor fluoxetine and the benzodiazepine diazepam, respectively. A single administration of fluoxetine (18 mg/kg; i.p.) produced a higher increase in hippocampal extracellular serotonin levels, and a greater antidepressant-like effect in the tail suspension test in Cx43 knock-down (KD) mice bred on a C57BL/6 background compared to their wild-type littermates. Similarly, in outbred Swiss wild-type mice, the intra-hippocampal injection of a shRNA-Cx43 or the acute systemic injection of the Cxs inhibitor carbenoxolone (CBX: 10 mg/kg; i.p.) potentiated the antidepressant-like effects of fluoxetine. Evaluating the effects of such strategies on diazepam (0.5 mg/kg; i.p.), the results indicate that Cx43 KD mice or wild-types injected with a shRNA-Cx43 in the amygdala, but not in the hippocampus, attenuated the anxiolytic-like effects of this benzodiazepine in the elevated plus maze. The chronic systemic administration of CBX mimicked the latter observations. Collectively, these data pave the way to the development of potentiating strategies in the field of psychiatry based on the modulation of astroglial Cx43.
Substances chimiques
Anti-Anxiety Agents
0
Antidepressive Agents
0
Connexin 43
0
Serotonin Uptake Inhibitors
0
Fluoxetine
01K63SUP8D
Benzodiazepines
12794-10-4
Diazepam
Q3JTX2Q7TU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13440Informations de copyright
© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
Références
Cotter DR, Pariante CM, Everall IP. Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull. 2001;55:585-595.
Ongur D, Drevets WC, Price JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA. 1998;95:13290-13295.
Rajkowska G, Miguel-Hidalgo JJ, Wei J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999;45:1085-1098.
Chana G, Landau S, Beasley C, Everall IP, Cotter D. Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density. Biol Psychiatry. 2003;53:1086-1098.
Torres-Platas SG, Hercher C, Davoli MA, et al. Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides. Neuropsychopharmacology. 2011;36:2650-2658.
Altshuler LL, Abulseoud OA, Foland-Ross L, et al. Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder. Bipolar Disord. 2010;12:541-549.
Czeh B, Simon M, Schmelting B, Hiemke C, Fuchs E. Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology. 2006;31:1616-1626.
Gosselin RD, Gibney S, O'Malley D, Dinan TG, Cryan JF. Region specific decrease in glial fibrillary acidic protein immunoreactivity in the brain of a rat model of depression. Neuroscience. 2009;159:915-925.
Banasr M, Duman RS. Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry. 2008;64:863-870.
David J, Gormley S, McIntosh AL, et al. L-alpha-amino adipic acid provokes depression-like behaviour and a stress related increase in dendritic spine density in the pre-limbic cortex and hippocampus in rodents. Behav Brain Res. 2019;362:90-102.
Quesseveur G, Gardier AM, Guiard BP. The monoaminergic tripartite synapse: a putative target for currently available antidepressant drugs. Curr Drug Targets. 2013;14:1277-1294.
Rivera AD, Butt AM. Astrocytes are direct cellular targets of lithium treatment: novel roles for lysyl oxidase and peroxisome-proliferator activated receptor- γ as astroglial targets of lithium. Transl Psychiatry. 2019;9:211.
Giaume C, Theis M. Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res Rev. 2010;63:160-176.
Orellana JA, Stehberg J. Hemichannels: new roles in astroglial function. Front Physiol. 2014;5:193.
Kimelberg HK. Supportive or information-processing functions of the mature protoplasmic astrocyte in the mammalian CNS? A critical appraisal. Neuron Glia Biol. 2007;3:181-189.
Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009;32:421-431.
Ernst C, Nagy C, Kim S, et al. Dysfunction of astrocyte connexins 30 and 43 in dorsal lateral prefrontal cortex of suicide completers. Biol Psychiatry. 2011;70:312-319.
Miguel-Hidalgo JJ, Wilson BA, Hussain S, Meshram A, Rajkowska G, Stockmeier CA. Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression. J Psychiatr Res. 2014;55:101-109.
Nagy C, Suderman M, Yang J, et al. Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry. 2015;20:320-328.
Medina A, Watson SJ, Bunney W, et al. Evidence for alterations of the glial syncytial function in major depressive disorder. J Psychiatr Res. 2016;72:15-21.
Torres-Platas SG, Nagy C, Wakid M, Turecki G, Mechawar N. Glial fibrillary acidic protein is differentially expressed across cortical and subcortical regions in healthy brains and downregulated in the thalamus and caudate nucleus of depressed suicides. Mol Psychiatry. 2016;21:509-515.
Miguel-Hidalgo JJ, Moulana M, Deloach PH, Rajkowska G. Chronic unpredictable stress reduces immunostaining for connexins 43 and 30 and myelin basic protein in the rat prelimbic and orbitofrontal cortices. Chronic Stress. 2018;2:247054701881418.
Ren Q, Wang ZZ, Chu SF, Xia CY, Chen NH. Gap junction channels as potential targets for the treatment of major depressive disorder. Psychopharmacology. 2018;235:1-12.
Sun JD, Liu Y, Yuan YH, Li J, Chen NH. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats. Neuropsychopharmacology. 2012;37:1305-1320.
Quesseveur G, Portal B, Basile JA, et al. Attenuated levels of hippocampal connexin 43 and its phosphorylation correlate with antidepressant- and anxiolytic-like activities in mice. Front Cell Neurosci. 2015;9:490.
Huang D, Li C, Zhang W, Qin J, Jiang W, Hu C. Dysfunction of astrocytic connexins 30 and 43 in the medial prefrontal cortex and hippocampus mediates depressive-like behaviours. Behav Brain Res. 2019;372:111950.
Jeanson T, Duchene A, Richard D, et al. Potentiation of amitriptyline anti-hyperalgesic-like action by astroglial connexin 43 inhibition in neuropathic rats. Sci Rep. 2016;6:38766.
Morioka N, Suekama K, Zhang FF, et al. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via activation of the p38 and c-Fos/AP-1 signalling pathway. Br J Pharmacol. 2014;171:2854-2867.
Cryan JF, Mombereau C, Vassout A. The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice. Neurosci Biobehav Rev. 2005;29:571-625.
Colin A, Faideau M, Dufour N, et al. Engineered lentiviral vector targeting astrocytes in vivo. Glia. 2009;57:667-679.
Kurt M, Arik AC, Celik S. The effects of sertraline and fluoxetine on anxiety in the elevated plus-maze test in mice. J Basic Clin Physiol Pharmacol. 2000;11:173-180.
Knobelman DA, Hen R, Blendy JA, Lucki I. Regional patterns of compensation following genetic deletion of either 5-hydroxytryptamine(1A) or 5-hydroxytryptamine(1B) receptor in the mouse. J Pharmacol Exp Ther. 2001;298:1092-1100.
Malagie I, David DJ, Jolliet P, Hen R, Bourin M, Gardier AM. Improved efficacy of fluoxetine in increasing hippocampal 5-hydroxytryptamine outflow in 5-HT(1B) receptor knock-out mice. Eur J Pharmacol. 2002;443:99-104.
Parsons LH, Kerr TM, Tecott LH. 5-HT(1A) receptor mutant mice exhibit enhanced tonic, stress-induced and fluoxetine-induced serotonergic neurotransmission. J Neurochem. 2001;77:607-617.
Zemdegs J, Martin H, Pintana H, et al. Metformin promotes anxiolytic and antidepressant-like responses in insulin-resistant mice by decreasing circulating branched-chain amino acids. J Neurosci. 2019;39:5935-5948.
Fox MA, Andrews AM, Wendland JR, Lesch KP, Holmes A, Murphy DL. A pharmacological analysis of mice with a targeted disruption of the serotonin transporter. Psychopharmacology. 2007;195:147-166.
Guiard BP, Mansari ME, Murphy DL, Blier P. Altered response to the selective serotonin reuptake inhibitor escitalopram in mice heterozygous for the serotonin transporter: an electrophysiological and neurochemical study. Int J Neuropsychopharmacol. 2012;15:349-361.
Mitchell NC, Gould GG, Koek W, Daws LC. Ontogeny of SERT expression and antidepressant-like response to escitalopram in wild-type and SERT mutant mice. J Pharmacol Exp Ther. 2016;358:271-281.
Murphy DL, Lerner A, Rudnick G, Lesch KP. Serotonin transporter: gene, genetic disorders, and pharmacogenetics. Mol Interv. 2004;4:109-123.
Blier P, de Montigny C. Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse. 1987;1:470-480.
Bortolozzi A, Castane A, Semakova J, et al. Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects. Mol Psychiatry. 2012;17:612-623.
Guilloux JP, David DJ, Xia L, et al. Characterization of 5-HT(1A/1B)-/- mice: an animal model sensitive to anxiolytic treatments. Neuropharmacology. 2011;61:478-488.
Rainer Q, Nguyen HT, Quesseveur G, Gardier AM, David DJ, Guiard BP. Functional status of somatodendritic serotonin 1A autoreceptor after long-term treatment with fluoxetine in a mouse model of anxiety/depression based on repeated corticosterone administration. Mol Pharmacol. 2012;81:106-112.
Richardson-Jones JW, Craige CP, Guiard BP, et al. 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron. 2010;65:40-52.
Jin ZL, Chen XF, Ran YH, et al. Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function. Sci Rep. 2017;7:8631.
Rajkowska G, Stockmeier CA. Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets. 2013;14:1225-1236.
Lucki I, Dalvi A, Mayorga AJ. Sensitivity to the effects of pharmacologically selective antidepressants in different strains of mice. Psychopharmacology. 2001;155:315-322.
Yalcin I, Belzung C, Surget A. Mouse strain differences in the unpredictable chronic mild stress: a four-antidepressant survey. Behav Brain Res. 2008;193:140-143.
Fatemi SH, Folsom TD, Reutiman TJ, Pandian T, Braun NN, Haug K. Chronic psychotropic drug treatment causes differential expression of connexin 43 and GFAP in frontal cortex of rats. Schizophr Res. 2008;104:127-134.
Mostafavi H, Khaksarian M, Joghataei MT, et al. Fluoxetin upregulates connexin 43 expression in astrocyte. Basic Clin Neurosci. 2014;5:74-79.
Takeuchi H, Mizoguchi H, Doi Y, et al. Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease. PLoS ONE. 2011;6:e21108.
Zhang X-M, Wang L-Z, He BO, et al. The gap junction inhibitor INI-0602 attenuates mechanical allodynia and depression-like behaviors induced by spared nerve injury in rats. NeuroReport. 2019;30:369-377.
Cao X, Li LP, Wang Q, et al. Astrocytes-derived ATP modulates depressive-like behaviors. Nat Med. 2013;19:773-777.
Kinoshita M, Hirayama Y, Fujishita K, et al. Anti-depressant fluoxetine reveals its therapeutic effect via astrocytes. EBioMedicine. 2018;32:72-83.
Ni M, He J-G, Zhou H-Y, et al. Pannexin-1 channel dysfunction in the medial prefrontal cortex mediates depressive-like behaviors induced by chronic social defeat stress and administration of mefloquine in mice. Neuropharmacology. 2018;137:256-267.
Dhanesha N, Joharapurkar A, Shah G, et al. Inhibition of 11beta-hydroxysteroid dehydrogenase 1 by carbenoxolone affects glucose homeostasis and obesity in db/db mice. Clin Exp Pharmacol Physiol. 2012;39:69-77.
Xia CY, Wang ZZ, Zhang Z, et al. Corticosterone impairs gap junctions in the prefrontal cortical and hippocampal astrocytes via different mechanisms. Neuropharmacology. 2018;131:20-30.
Soro A, Panarelli M, Holloway CD, Fraser R, Kenyon CJ. In vivo and in vitro effects of carbenoxolone on glucocorticoid receptor binding and glucocorticoid activity. Steroids. 1997;62:388-394.
Bale TL, Abel T, Akil H, et al. The critical importance of basic animal research for neuropsychiatric disorders. Neuropsychopharmacol. 2019;44:1349-1353.
Moret C. Combination/augmentation strategies for improving the treatment of depression. Neuropsychiatr Dis Treat. 2005;1:301-309.
Olivier JD, Blom T, Arentsen T, Homberg JR. The age-dependent effects of selective serotonin reuptake inhibitors in humans and rodents: A review. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1400-1408.
Liu J, Garza JC, Bronner J, Kim CS, Zhang W, Lu XY. Acute administration of leptin produces anxiolytic-like effects: a comparison with fluoxetine. Psychopharmacology. 2010;207:535-545.
Paterson NE, Iwunze M, Davis SF, Malekiani SA, Hanania T. Comparison of the predictive validity of the mirror chamber and elevated plus maze tests in mice. J Neurosci Methods. 2010;188:62-70.
Iversen SD. 5-HT and anxiety. Neuropharmacology. 1984;23:1553-1560.
Tiller J, Schweitzer I, Maguire K, Davies B. A sequential double-blind controlled study of moclobemide and diazepam in patients with atypical depression. J Affect Disord. 1989;16:181-187.
Petit-Demouliere B, Masse F, Cogrel N, Hascoet M, Bourin M. Brain structures implicated in the four-plate test in naive and experienced Swiss mice using injection of diazepam and the 5-HT2A agonist DOI. Behav Brain Res. 2009;204:200-205.
Sigel E, Baur R. Allosteric modulation by benzodiazepine receptor ligands of the GABAA receptor channel expressed in Xenopus oocytes. J Neurosci. 1988;8:289-295.
Delaney AJ, Sah P. GABA receptors inhibited by benzodiazepines mediate fast inhibitory transmission in the central amygdala. J Neurosci. 1999;19:9698-9704.
Ransom CB, Ye Z, Spain WJ, Richerson GB. Modulation of tonic GABA currents by anion channel and connexin hemichannel antagonists. Neurochem Res. 2017;42:2551-2559.
Verkhratsky A, Nedergaard M. The homeostatic astroglia emerges from evolutionary specialization of neural cells. Philos Trans R Soc Lond B Biol Sci. 2016;371.
Lee M, McGeer EG, McGeer PL. Mechanisms of GABA release from human astrocytes. Glia. 2011;59:1600-1611.
Lee S, Yoon BE, Berglund K, et al. Channel-mediated tonic GABA release from glia. Science. 2010;330:790-796.
Mayorquin LC, Rodriguez AV, Sutachan JJ, Albarracin SL. Connexin-mediated functional and metabolic coupling between astrocytes and neurons. Front Mol Neurosci. 2018;11:118.
Theis M, Jauch R, Zhuo L, et al. Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin43. J Neurosci. 2003;23:766-776.
Persson PB. Good publication practice in physiology. Acta Physiol (Oxf). 2015;215:163-164.
O'Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology. 2007;192:357-371.
Griebel G, Belzung C, Perrault G, Sanger DJ. Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice. Psychopharmacology. 2000;148:164-170.
Gareri P, Condorelli D, Belluardo N, et al. Anticonvulsant effects of carbenoxolone in genetically epilepsy prone rats (GEPRs). Neuropharmacology. 2004;47:1205-1216.
Merienne N, Delzor A, Viret A, et al. Gene transfer engineering for astrocyte-specific silencing in the CNS. Gene Ther. 2015;22:830-839.