{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:27:12Z","timestamp":1786552032872,"version":"build-2736575974"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South Dakota State University (SDSU) Research Foundation","award":["NIMH R01 MH122954"],"award-info":[{"award-number":["NIMH R01 MH122954"]}]},{"name":"South Dakota State University (SDSU) Research Foundation","award":["NIH NIGMS U54GM128729"],"award-info":[{"award-number":["NIH NIGMS U54GM128729"]}]},{"name":"Department of Pharmaceutical Sciences of SDSU","award":["NIMH R01 MH122954"],"award-info":[{"award-number":["NIMH R01 MH122954"]}]},{"name":"Department of Pharmaceutical Sciences of SDSU","award":["NIH NIGMS U54GM128729"],"award-info":[{"award-number":["NIH NIGMS U54GM128729"]}]},{"name":"Department of Veterans Affairs Merit Review Award","award":["NIMH R01 MH122954"],"award-info":[{"award-number":["NIMH R01 MH122954"]}]},{"name":"Department of Veterans Affairs Merit Review Award","award":["NIH NIGMS U54GM128729"],"award-info":[{"award-number":["NIH NIGMS U54GM128729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of \u03b17 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an \u03b17 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction. The effects of ANA12, a TrkB receptor antagonist, on LPS-induced cognitive deficit and depressive-like behaviors were determined using the Y-maze, tail suspension test (TST), and forced swim test (FST). Pharmacological interactions between PNU120596 and ANA12 were also examined. Experiments were conducted in male C57BL\/6J mice. LPS administration (1 mg\/kg) resulted in increased expression of BDNF and the NKCC1\/KCC2 ratio and decreased expression of KCC2 in the hippocampus and prefrontal cortex. PNU120596 pretreatment (4 mg\/kg) attenuated the LPS-induced increase in the expression of BDNF and NKCC1\/KCC2 ratio and the reduction in KCC2 expression in these brain regions. In addition, ANA12 (0.25 or 0.50 mg\/kg) reduced the LPS-induced cognitive deficit and depressive-like behaviors measured by a reduced spontaneous alternation in the Y-maze and increased immobility duration in TST and FST. Coadministration of PNU120596 (1 mg\/kg) and ANA12 (0.25 mg\/kg) prevented the LPS-induced cognitive deficit and depressive-like behaviors. Overall, PNU120596 prevented the LPS-induced depressive-like behavior by likely decreasing neuronal excitability via targeting microglial \u03b17 nAChR in the hippocampus and prefrontal cortex.<\/jats:p>","DOI":"10.3390\/brainsci14030290","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T09:39:31Z","timestamp":1710841171000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The \u03b1-7 Nicotinic Receptor Positive Allosteric Modulator Alleviates Lipopolysaccharide Induced Depressive-like Behavior by Regulating Microglial Function, Trophic Factor, and Chloride Transporters in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4007-4023","authenticated-orcid":false,"given":"Sami","family":"Alzarea","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amna","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Ronan","sequence":"additional","affiliation":[{"name":"Research Service, Sioux Falls VA Healthcare System, Sioux Falls, SD 57105, USA"},{"name":"Department of Psychiatry and Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kabirullah","family":"Lutfy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6289-5386","authenticated-orcid":false,"given":"Shafiqur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA"},{"name":"Research Service, Sioux Falls VA Healthcare System, Sioux Falls, SD 57105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1007\/s00213-019-05190-7","article-title":"Lipocalin-2 is dispensable in inflammation-induced sickness and depression-like behavior","volume":"236","author":"Vichaya","year":"2019","journal-title":"Psychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","article-title":"The bidirectional relationship of depression and inflammation: Double trouble","volume":"107","author":"Beurel","year":"2020","journal-title":"Neuron"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.biopsych.2022.11.003","article-title":"Inflammation-related functional and structural dysconnectivity as a pathway to psychopathology","volume":"93","author":"Goldsmith","year":"2023","journal-title":"Biol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/ejn.14720","article-title":"Neuroinflammation and depression: A review","volume":"53","author":"Troubat","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41380-019-0474-5","article-title":"Peripheral cytokine levels and response to antidepressant treatment in depression: A systematic review and meta-analysis","volume":"25","author":"Liu","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2174\/1570159X15666171123201142","article-title":"Imaging the role of inflammation in mood and anxiety-related disorders","volume":"16","author":"Felger","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1038\/npp.2011.132","article-title":"The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: A meta-analysis","volume":"36","author":"Hannestad","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.biopsych.2004.02.009","article-title":"Cytokines and psychopathology: Lessons from interferon-alpha","volume":"56","author":"Capuron","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.biopsych.2009.03.015","article-title":"Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity","volume":"66","author":"Harrison","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.biopsych.2007.12.007","article-title":"Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans","volume":"63","author":"Brydon","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Grigoleit, J.S., Kullmann, J.S., Wolf, O.T., Hammes, F., Wegner, A., Jablonowski, S., Engler, H., Gizewski, E., Oberbeck, R., and Schedlowski, M. (2011). Dose-dependent effects of endotoxin on neurobehavioral functions in humans. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028330"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.biopsych.2010.06.010","article-title":"Inflammation-induced anhedonia: Endotoxin reduces ventral striatum responses to reward","volume":"68","author":"Eisenberger","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.bbi.2005.04.010","article-title":"Low-dose endotoxemia and human neuropsychological functions","volume":"19","author":"Krabbe","year":"2005","journal-title":"Brain Behav. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bbr.2009.07.026","article-title":"Medial prefrontal administration of MK-801 impairs T-maze discrimination reversal learning in weanling rats","volume":"205","author":"Watson","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e918","DOI":"10.1038\/tp.2016.200","article-title":"Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation","volume":"6","author":"Parrott","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/sj.mp.4002148","article-title":"Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice","volume":"14","author":"Lawson","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"408","DOI":"10.2174\/1570159X17666191113101629","article-title":"The potential role of dysfunctions in neuron-microglia communication in the pathogenesis of brain disorders","volume":"18","author":"Chamera","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1002\/glia.23934","article-title":"Neuronal brain-derived neurotrophic factor manipulates microglial dynamics","volume":"69","author":"Onodera","year":"2021","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s12974-022-02492-0","article-title":"Microglia in depression: An overview of microglia in the pathogenesis and treatment of depression","volume":"19","author":"Wang","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1002\/jnr.22101","article-title":"A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth","volume":"87","author":"Alfa","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuroscience.2006.06.002","article-title":"Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice","volume":"142","author":"Chan","year":"2006","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106145","DOI":"10.1016\/j.phrs.2022.106145","article-title":"Stress induced microglial activation contributes to depression","volume":"179","author":"Li","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.neubiorev.2021.09.018","article-title":"Microglia and BDNF at the crossroads of stressor related disorders: Towards a unique trophic phenotype","volume":"131","author":"Prowse","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1242\/dev.01702","article-title":"NF-kappaB signalling regulates the growth of neural processes in the developing PNS and CNS","volume":"132","author":"Gutierrez","year":"2005","journal-title":"Development"},{"key":"ref_25","first-page":"121","article-title":"Role of brain-derived neurotrophic factor and NF-kappaB in neuronal plasticity and survival: From genes to phenotype","volume":"22","author":"Marini","year":"2004","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1083\/jcb.200209011","article-title":"BDNF-induced TrkB activation down-regulates the K+-Cl\u2212 cotransporter KCC2 and impairs neuronal Cl\u2212 extrusion","volume":"159","author":"Rivera","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6996","DOI":"10.1523\/JNEUROSCI.5268-07.2008","article-title":"Posttraumatic GABA(A)-mediated [Ca2+]i increase is essential for the induction of brain-derived neurotrophic factor-dependent survival of mature central neurons","volume":"28","author":"Shulga","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104925","DOI":"10.1016\/j.neuint.2020.104925","article-title":"Ion channels and transporters in microglial function in physiology and brain diseases","volume":"142","author":"Luo","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.bbi.2020.04.004","article-title":"Interleukin-18 from neurons and microglia mediates depressive behaviors in mice with post-stroke depression","volume":"88","author":"Wu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1159\/000446114","article-title":"Chronic unpredictable mild stress induces loss of GABA inhibition in corticotrophin-releasing hormone-expressing neurons through NKCC1 upregulation","volume":"104","author":"Gao","year":"2016","journal-title":"Neuroendocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5216","DOI":"10.1523\/JNEUROSCI.4626-11.2012","article-title":"Transcript-specific associations of SLC12A5 (KCC2) in human prefrontal cortex with development, schizophrenia, and affective disorders","volume":"32","author":"Tao","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1152\/physrev.00025.2021","article-title":"Chloride transporters controlling neuronal excitability","volume":"103","author":"Pressey","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8805","DOI":"10.1523\/JNEUROSCI.6159-08.2009","article-title":"Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer\u2019s disease","volume":"29","author":"Dziewczapolski","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2174\/138161210790170094","article-title":"Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: From animal models to human pathophysiology","volume":"16","author":"Thomsen","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.tips.2006.07.004","article-title":"Brain nicotinic acetylcholine receptors: Native subtypes and their relevance","volume":"27","author":"Gotti","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/sj.bjp.0707264","article-title":"The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation","volume":"151","author":"Ulloa","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.pnpbp.2018.05.018","article-title":"Effects of alpha-7 nicotinic allosteric modulator PNU 120596 on depressive-like behavior after lipopolysaccharide administration in mice","volume":"86","author":"Alzarea","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.5582\/ddt.2017.01038","article-title":"The alpha7 nicotinic acetylcholine receptor positive allosteric modulator attenuates lipopolysaccharide-induced activation of hippocampal IkappaB and CD11b gene expression in mice","volume":"11","author":"Abbas","year":"2017","journal-title":"Drug Discov. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/bs.pmbts.2019.06.010","article-title":"Glial mechanisms underlying major depressive disorder: Potential therapeutic opportunities","volume":"167","author":"Rahman","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00429-008-0189-x","article-title":"Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression","volume":"213","author":"Drevets","year":"2008","journal-title":"Brain Struct. Funct."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0893-133X(99)00146-3","article-title":"Nicotinic receptors in the brain. Links between molecular biology and behavior","volume":"22","author":"Picciotto","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bbr.2019.03.019","article-title":"Alpha-7 nicotinic receptor allosteric modulator PNU120596 prevents lipopolysaccharide-induced anxiety, cognitive deficit and depression-like behaviors in mice","volume":"366","author":"Alzarea","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1124\/jpet.108.150151","article-title":"Activation and desensitization of nicotinic alpha7-type acetylcholine receptors by benzylidene anabaseines and nicotine","volume":"329","author":"Papke","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.bcp.2011.05.001","article-title":"Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: Advantages and limitations","volume":"82","author":"Williams","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1007\/s00213-014-3472-y","article-title":"The effects of lobeline on nicotine withdrawal-induced depression-like behavior in mice","volume":"231","author":"Roni","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pnpbp.2012.11.011","article-title":"Antidepressant-like effects of lobeline in mice: Behavioral, neurochemical, and neuroendocrine evidence","volume":"41","author":"Roni","year":"2013","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.alcohol.2017.01.015","article-title":"Lobeline attenuates ethanol abstinence-induced depression-like behavior in mice","volume":"61","author":"Roni","year":"2017","journal-title":"Alcohol"},{"key":"ref_48","first-page":"3295","article-title":"Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation","volume":"56","author":"Doorduin","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1111\/j.1460-9568.2009.06898.x","article-title":"NF-kappaB-dependent regulation of brain-derived neurotrophic factor in hippocampal neurons by X-linked inhibitor of apoptosis protein","volume":"30","author":"Kairisalo","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.1120972","article-title":"Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress","volume":"311","author":"Berton","year":"2006","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.biopsych.2003.08.003","article-title":"Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: A role in depression","volume":"54","author":"Eisch","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/ejn.14630","article-title":"Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants","volume":"53","author":"Duman","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.neuroscience.2014.03.025","article-title":"Antidepressant-like effect of nitric oxide synthase inhibitors and sildenafil against lipopolysaccharide-induced depressive-like behavior in mice","volume":"268","author":"Tomaz","year":"2014","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/jnr.20789","article-title":"Early social enrichment augments adult hippocampal BDNF levels and survival of BrdU-positive cells while increasing anxiety- and \u201cdepression\u201d-like behavior","volume":"83","author":"Branchi","year":"2006","journal-title":"J. Neurosci. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13208","DOI":"10.1073\/pnas.0605180103","article-title":"Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects","volume":"103","author":"Govindarajan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/S0028-3908(02)00220-4","article-title":"Regulation of cAMP phosphodiesterase mRNAs expression in rat brain by acute and chronic fluoxetine treatment. An in situ hybridization study","volume":"43","author":"Miro","year":"2002","journal-title":"Neuropharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbi.2005.04.005","article-title":"Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats","volume":"20","author":"Guan","year":"2006","journal-title":"Brain Behav. Immun."},{"key":"ref_58","first-page":"e13739","article-title":"The role of the kynurenine pathway and quinolinic acid in adolescent major depressive disorder","volume":"75","author":"Kandemir","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Alzarea, S., Abbas, M., Ronan, P.J., Lutfy, K., and Rahman, S. (2022). The Effect of an \u03b1-7 Nicotinic Allosteric Modulator PNU120596 and NMDA Receptor Antagonist Memantine on Depressive-like Behavior Induced by LPS in Mice: The Involvement of Brain Microglia. Brain Sci., 12.","DOI":"10.3390\/brainsci12111493"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1002\/2211-5463.12270","article-title":"A G protein-coupled \u03b17 nicotinic receptor regulates signaling and TNF-\u03b1 release in microglia","volume":"7","author":"King","year":"2017","journal-title":"FEBS Open Bio."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s12974-017-0967-6","article-title":"Anti-inflammatory effects of astroglial \u03b17 nicotinic acetylcholine receptors are mediated by inhibition of the NF-\u03baB pathway and activation of the Nrf2 pathway","volume":"14","author":"Patel","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"429815","DOI":"10.1155\/2013\/429815","article-title":"Microglia control neuronal network excitability via BDNF signalling","volume":"2013","author":"Ferrini","year":"2013","journal-title":"Neural Plast."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/mp.2010.120","article-title":"The GABAergic deficit hypothesis of major depressive disorder","volume":"16","author":"Luscher","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_64","first-page":"366","article-title":"Effects of \u03b17 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator on BDNF, NKCC1 and KCC2 Expression in the Hippocampus following Lipopolysaccharide-Induced Allodynia and Hyperalgesia in a Mouse Model of Inflammatory Pain","volume":"20","author":"Abbas","year":"2021","journal-title":"CNS Neurol. Disord. Drug Targets (Former. Curr. Drug Targets CNS Neurol. Disord.)"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2","DOI":"10.7243\/2052-8000-2-2","article-title":"Deficits in KCC2 and activation of the HPA axis lead to depression-like behavior following social defeat","volume":"2","author":"Miller","year":"2014","journal-title":"Horm. Stud."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fnmol.2019.00012","article-title":"Bumetanide Prevents Brain Trauma-Induced Depressive-Like Behavior","volume":"12","author":"Goubert","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.tins.2015.08.001","article-title":"Depression as a microglial disease","volume":"38","author":"Yirmiya","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1742-2094-10-16","article-title":"Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia","volume":"10","author":"Gomes","year":"2013","journal-title":"J. Neuroinflamm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/(SICI)1097-4547(19971215)50:6<1023::AID-JNR13>3.0.CO;2-5","article-title":"Lipopolysaccharide enhances synthesis of brain-derived neurotrophic factor in cultured rat microglia","volume":"50","author":"Miwa","year":"1997","journal-title":"J. Neurosci. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","article-title":"Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor","volume":"155","author":"Parkhurst","year":"2013","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0896-6273(00)81010-7","article-title":"Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism","volume":"20","author":"Tao","year":"1998","journal-title":"Neuron"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"961276","DOI":"10.3389\/fncel.2022.961276","article-title":"Analysis of microglial BDNF function and expression in the motor cortex","volume":"16","author":"Honey","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1124\/mol.116.104240","article-title":"Understanding the Bases of Function and Modulation of alpha7 Nicotinic Receptors: Implications for Drug Discovery","volume":"90","author":"Corradi","year":"2016","journal-title":"Mol. Pharmacol"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.tips.2018.01.002","article-title":"Beyond the Channel: Metabotropic Signaling by Nicotinic Receptors","volume":"39","author":"Kabbani","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1007\/s00213-015-4062-3","article-title":"Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression","volume":"232","author":"Zhang","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_76","first-page":"pyu077","article-title":"Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation","volume":"18","author":"Zhang","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3389\/fpsyt.2018.00655","article-title":"Recognition and Treatment of Cognitive Dysfunction in Major Depressive Disorder","volume":"9","author":"Zuckerman","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.lfs.2010.09.004","article-title":"Assessment of spatial memory in mice","volume":"87","author":"Sharma","year":"2010","journal-title":"Life Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bbr.2006.10.006","article-title":"Stress, prefrontal cortex and environmental enrichment: Studies on dopamine and acetylcholine release and working memory performance in rats","volume":"176","author":"Segovia","year":"2007","journal-title":"Behav. Brain Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/3\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:59Z","timestamp":1760105759000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/3\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":79,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["brainsci14030290"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14030290","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]}}}