Sistema de Eventos Acadêmicos da UFMT, X Mostra da Pós-Graduação: Direitos Humanos, trabalho coletivo e redes de pesquisa na Pós Graduação

Tamanho da fonte: 
EFEITO NEUROPROTETOR DA ROSIGLITAZONA NO MODELO DE COMPORTAMENTO DEPRESSIVO INDUZIDO POR LIPOPOLISSACARÍDEO (LPS) EM CAMUNDONGOS.
Íris Juliana Viotto Stupp, Eguiberto Bernardes Fraga Júnior, Diego L Doneda, Samuel Vandresen Filho, Ziliani Buss, Eric Taniguti, Yago Ferreira

Última alteração: 05-10-18

Resumo


A depressão é um distúrbio psiquiátrico grave e comum, caracterizado por humor deprimido, anedonia e associado a disfunções cognitivas. Estudos anteriores mostraram que a neuroinflamação induzida pelo lipopolissacarídeo (LPS) causa comportamento depressivo e déficits cognitivos em roedores. A rosiglitazona é um agonista do receptor ativado por proliferador de peroxissoma gama (PPAR-γ) usado para o tratamento do diabetes tipo II. Diversos estudos demonstraram que a rosilgitazona também exerce efeitos neuroprotetores em modelos experimentais de doenças neurológicas e psiquiátricas. No entanto, os efeitos da rosiglitazona no comportamento tipo depressivo induzido por LPS, deficiências de memória e neuroinflamação são desconhecidos. Assim, neste estudo, objetivamos avaliar os efeitos protetores do tratamento com rosiglitazona sobre o comportamento depressivo induzido por LPS e déficits cognitivos em camundongos. Os animais foram tratados com rosiglitazona (5 mg / kg, v.o.) uma hora antes da administração de LPS (0,5 mg / kg, i.p.). Um dia após a infusão de LPS, os camundongos foram submetidos aos testes comportamentais e, posteriormente, foram realizadas determinações bioquímicas. A rosiglitazona impediu o aumento da imobilidade induzido por LPS nos testes de suspensão da cauda e nado forçado. A rosiglitazona impediu significativamente a diminuição das alternações espontâneas induzidas pelo LPS no teste do labirinto em Y. Na tarefa de esquiva inibitória, o LPS diminuiu as latências, que foram melhoradas pelo tratamento com rosilgitazona. No teste de campo aberto, nenhuma alteração na deambulação foi observada. A rosiglitazona preveniu o aumento do TNF-α induzido por LPS e a redução dos níveis de BDNF no hipocampo. A rosiglitazona também melhorou o aumento da peroxidação lipídica induzido por LPS e a redução dos níveis de glutationa no hipocampo. Nossos achados sugerem que a rosiglitazona pode possuir efeitos neuroprotetores no comportamento tipo depressivo induzido por LPS e déficits cognitivos reduz a neuroinflamação, dano oxidativo e normalização dos níveis de BDNF.

Palavras-chave


: Rosiglitazona; lipopolissacarídeo; depressão; memória; factor de necrose tumoral-α; neurotrófico derivado do cérebro

Referências


Adebesin, A., O. A. Adeoluwa, A. T. Eduviere and S. Umukoro (2017). "Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice." J Psychiatr Res 94: 29-35.Amidfar, M., Y. K. Kim and O. Wiborg (2018). "Effectiveness of memantine on depression-like behavior, memory deficits and brain mRNA levels of BDNF and TrkB in rats subjected to repeated unpredictable stress." Pharmacol Rep 70(3): 600-606.Aydemir, O., A. Deveci and F. Taneli (2005). "The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study." Prog Neuropsychopharmacol Biol Psychiatry 29(2): 261-265.Bajpai, A., A. K. Verma, M. Srivastava and R. Srivastava (2014). "Oxidative stress and major depression." J Clin Diagn Res 8(12): CC04-07.Belarbi, K., T. Jopson, D. Tweedie, C. Arellano, W. Luo, N. H. Greig and S. Rosi (2012). "TNF-alpha protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation." J Neuroinflammation 9: 23.Bordet, R., T. Ouk, O. Petrault, P. Gele, S. Gautier, M. Laprais, D. Deplanque, P. Duriez, B. Staels, J. C. Fruchart and M. Bastide (2006). "PPAR: a new pharmacological target for neuroprotection in stroke and neurodegenerative diseases." Biochem Soc Trans 34(Pt 6): 1341-1346.Bortolato, B., A. F. Carvalho, J. K. Soczynska, G. I. Perini and R. S. McIntyre (2015). "The Involvement of TNF-alpha in Cognitive Dysfunction Associated with Major Depressive Disorder: An Opportunity for Domain Specific Treatments." Curr Neuropharmacol 13(5): 558-576.Brocardo Pde, S., J. Budni, K. R. Lobato, M. P. Kaster and A. L. Rodrigues (2008). "Antidepressant-like effect of folic acid: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway." Eur J Pharmacol 598(1-3): 37-42.Buss Zda, S., Y. S. Medeiros and T. S. Frode (2012). "PPAR-gamma agonist rosiglitazone attenuates the inflammation caused by carrageenan in the mouse model of pleurisy." Inflammation 35(1): 280-288.Caraci, F., S. F. Spampinato, M. G. Morgese, F. Tascedda, M. G. Salluzzo, M. C. Giambirtone, G. Caruso, A. Munafo, S. A. Torrisi, G. M. Leggio, L. Trabace, F. Nicoletti, F. Drago, M. A. Sortino and A. Copani (2018). "Neurobiological links between depression and AD: The role of TGF-beta1 signaling as a new pharmacological target." Pharmacol Res 130: 374-384.Cheng, Y., R. M. Rodriguiz, S. R. Murthy, V. Senatorov, E. Thouennon, N. X. Cawley, D. K. Aryal, S. Ahn, B. Lecka-Czernik, W. C. Wetsel and Y. P. Loh (2015). "Neurotrophic factor-alpha1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone." Mol Psychiatry 20(6): 744-754.Chowdhury, A. A., N. B. Gawali, P. Shinde, R. Munshi and A. R. Juvekar (2018). "Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor." Cytokine 110: 78-86.Colle, R., D. de Larminat, S. Rotenberg, F. Hozer, P. Hardy, C. Verstuyft, B. Feve and E. Corruble (2017). "PPAR-gamma Agonists for the Treatment of Major Depression: A Review." Pharmacopsychiatry 50(2): 49-55.Dantzer, R. (2009). "Cytokine, sickness behavior, and depression." Immunol Allergy Clin North Am 29(2): 247-264.Dantzer, R., J. C. O'Connor, G. G. Freund, R. W. Johnson and K. W. Kelley (2008). "From inflammation to sickness and depression: when the immune system subjugates the brain." Nat Rev Neurosci 9(1): 46-56.Dolatabadi, H. R. D., M. R. Zarrindast, P. Reisi and M. Nasehi (2017). "The Effects of Pentoxifylline on Serum Levels of Interleukin 10 and Interferon Gamma and Memory Function in Lipopolysaccharide-induced Inflammation in Rats." Adv Biomed Res 6: 110.Dowlati, Y., N. Herrmann, W. Swardfager, H. Liu, L. Sham, E. K. Reim and K. L. Lanctot (2010). "A meta-analysis of cytokines in major depression." Biol Psychiatry 67(5): 446-457.Eissa Ahmed, A. A., N. M. Al-Rasheed and N. M. Al-Rasheed (2009). "Antidepressant-like effects of rosiglitazone, a PPARgamma agonist, in the rat forced swim and mouse tail suspension tests." Behav Pharmacol 20(7): 635-642.Ellman, G. L. (1959). "Tissue sulfhydryl groups." Arch Biochem Biophys 82(1): 70-77.Fruhauf-Perez, P. K., F. R. Temp, M. M. Pillat, C. Signor, A. L. Wendel, H. Ulrich, C. F. Mello and M. A. Rubin (2018). "Spermine protects from LPS-induced memory deficit via BDNF and TrkB activation." Neurobiol Learn Mem 149: 135-143.Garcia-Bueno, B., J. L. Madrigal, I. Lizasoain, M. A. Moro, P. Lorenzo and J. C. Leza (2005). "Peroxisome proliferator-activated receptor gamma activation decreases neuroinflammation in brain after stress in rats." Biol Psychiatry 57(8): 885-894.Ge, L., L. Liu, H. Liu, S. Liu, H. Xue, X. Wang, L. Yuan, Z. Wang and D. Liu (2015). "Resveratrol abrogates lipopolysaccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice." Eur J Pharmacol 768: 49-57.Hajjar, I., S. S. Hayek, F. C. Goldstein, G. Martin, D. P. Jones and A. Quyyumi (2018). "Oxidative stress predicts cognitive decline with aging in healthy adults: an observational study." J Neuroinflammation 15(1): 17.Heikkinen, S., J. Auwerx and C. A. Argmann (2007). "PPARgamma in human and mouse physiology." Biochim Biophys Acta 1771(8): 999-1013.Jangra, A., M. M. Lukhi, K. Sulakhiya, C. C. Baruah and M. Lahkar (2014). "Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice." Eur J Pharmacol 740: 337-345.Kaneko, Y. S., A. Ota, A. Nakashima, K. Mori, I. Nagatsu and T. Nagatsu (2012). "Regulation of oxidative stress in long-lived lipopolysaccharide-activated microglia." Clin Exp Pharmacol Physiol 39(7): 599-607.Kariharan, T., G. Nanayakkara, K. Parameshwaran, I. Bagasrawala, M. Ahuja, E. Abdel-Rahman, A. T. Amin, M. Dhanasekaran, V. Suppiramaniam and R. H. Amin (2015). "Central activation of PPAR-gamma ameliorates diabetes induced cognitive dysfunction and improves BDNF expression." Neurobiol Aging 36(3): 1451-1461.Khajevand-Khazaei, M. R., P. Ziaee, S. A. Motevalizadeh, M. Rohani, S. Afshin-Majd, T. Baluchnejadmojarad and M. Roghani (2018). "Naringenin ameliorates learning and memory impairment following systemic lipopolysaccharide challenge in the rat." Eur J Pharmacol 826: 114-122.Khallaf, W. A. I., B. A. S. Messiha, A. M. H. Abo-Youssef and N. S. El-Sayed (2017). "Protective effects of telmisartan and tempol on lipopolysaccharide-induced cognitive impairment, neuroinflammation, and amyloidogenesis: possible role of brain-derived neurotrophic factor." Can J Physiol Pharmacol 95(7): 850-860.Kim, D. H., T. M. Hung, K. H. Bae, J. W. Jung, S. Lee, B. H. Yoon, J. H. Cheong, K. H. Ko and J. H. Ryu (2006). "k." Eur J Pharmacol 542(1-3): 129-135.Kim, Y. E., C. J. Hwang, H. P. Lee, C. S. Kim, D. J. Son, Y. W. Ham, M. Hellstrom, S. B. Han, H. S. Kim, E. K. Park and J. T. Hong (2017). "Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB." Neuropharmacology 117: 21-32.Kim, Y. K., K. S. Na, A. M. Myint and B. E. Leonard (2016). "The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression." Prog Neuropsychopharmacol Biol Psychiatry 64: 277-284.Kreinin, A., S. Lisson, E. Nesher, J. Schneider, J. Bergman, K. Farhat, J. Farah, F. Lejbkowicz, G. Yadid, L. Raskin, I. Koman and A. Pinhasov (2015). "Blood BDNF level is gender specific in severe depression." PLoS One 10(5): e0127643.Kumar, P., R. K. Kaundal, S. More and S. S. Sharma (2009). "Beneficial effects of pioglitazone on cognitive impairment in MPTP model of Parkinson's disease." Behav Brain Res 197(2): 398-403.Lason, W., B. Budziszewska, A. Basta-Kaim, M. Kubera and M. Maes (2013). "New trends in the neurobiology and pharmacology of affective disorders." Pharmacol Rep 65(6): 1441-1450.Lee, B. H. and Y. K. Kim (2010). "The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment." Psychiatry Investig 7(4): 231-235.Lee, J. W., Y. K. Lee, D. Y. Yuk, D. Y. Choi, S. B. Ban, K. W. Oh and J. T. Hong (2008). "Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation." J Neuroinflammation 5: 37.Lee, Y. J., D. Y. Choi, I. S. Choi, K. H. Kim, Y. H. Kim, H. M. Kim, K. Lee, W. G. Cho, J. K. Jung, S. B. Han, J. Y. Han, S. Y. Nam, Y. W. Yun, J. H. Jeong, K. W. Oh and J. T. Hong (2012). "Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models." J Neuroinflammation 9: 35.Liao, L., X. D. Zhang, J. Li, Z. W. Zhang, C. C. Yang, C. L. Rao, C. J. Zhou, L. Zeng, L. B. Zhao, L. Fang, D. Y. Yang and P. Xie (2017). "Pioglitazone attenuates lipopolysaccharide-induced depression-like behaviors, modulates NF-kappaB/IL-6/STAT3, CREB/BDNF pathways and central serotonergic neurotransmission in mice." Int Immunopharmacol 49: 178-186.Lima, I. M. M., A. D. Peckham and S. L. Johnson (2018). "Cognitive deficits in bipolar disorders: Implications for emotion." Clin Psychol Rev 59: 126-136.Liu, L. P., T. H. Yan, L. Y. Jiang, W. Hu, M. Hu, C. Wang, Q. Zhang, Y. Long, J. Q. Wang, Y. Q. Li, M. Hu and H. Hong (2013). "Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain beta-amyloid through PPARgamma activation." Acta Pharmacol Sin 34(4): 455-463.Liu, Y., Y. Zhang, X. Zheng, T. Fang, X. Yang, X. Luo, A. Guo, K. A. Newell, X. F. Huang and Y. Yu (2018). "Galantamine improves cognition, hippocampal inflammation, and synaptic plasticity impairments induced by lipopolysaccharide in mice." J Neuroinflammation 15(1): 112.Lowry, O. H., N. J. Rosebrough, A. L. Farr and R. J. Randall (1951). "Protein measurement with the Folin phenol reagent." J Biol Chem 193(1): 265-275.Lucena, G. M., R. D. Prediger, M. V. Silva, S. N. Santos, J. F. Silva, A. R. Santos, M. S. Azevedo and V. M. Ferreira (2013). "Ethanolic extract from bulbs of Cipura paludosa reduced long-lasting learning and memory deficits induced by prenatal methylmercury exposure in rats." Dev Cogn Neurosci 3: 1-10.Ma, L., K. A. Demin, T. O. Kolesnikova, S. L. Kharsko, X. Zhu, X. Yuan, C. Song, D. A. Meshalkina, B. E. Leonard, L. Tian and A. V. Kalueff (2017). "Animal inflammation-based models of depression and their application to drug discovery." Expert Opin Drug Discov 12(10): 995-1009.Madeira, J. M., S. M. Schindler and A. Klegeris (2015). "A new look at auranofin, dextromethorphan and rosiglitazone for reduction of glia-mediated inflammation in neurodegenerative diseases." Neural Regen Res 10(3): 391-393.Mandrekar-Colucci, S., A. Sauerbeck, P. G. Popovich and D. M. McTigue (2013). "PPAR agonists as therapeutics for CNS trauma and neurological diseases." ASN Neuro 5(5): e00129.Matrisciano, F., S. Bonaccorso, A. Ricciardi, S. Scaccianoce, I. Panaccione, L. Wang, A. Ruberto, R. Tatarelli, F. Nicoletti, P. Girardi and R. C. Shelton (2009). "Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine." J Psychiatr Res 43(3): 247-254.Mello, B. S., A. S. Monte, R. S. McIntyre, J. K. Soczynska, C. S. Custodio, R. C. Cordeiro, J. H. Chaves, S. M. Vasconcelos, H. V. Nobre, Jr., F. C. Florenco de Sousa, T. N. Hyphantis, A. F. Carvalho and D. S. Macedo (2013). "Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration." J Psychiatr Res 47(10): 1521-1529.Mirahmadi, S. M., A. Shahmohammadi, A. M. Rousta, M. R. Azadi, J. Fahanik-Babaei, T. Baluchnejadmojarad and M. Roghani (2018). "Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects." Cytokine 104: 151-159.Mishra, J., T. Chaudhary and A. Kumar (2014). "Rosiglitazone synergizes the neuroprotective effects of valproic acid against quinolinic acid-induced neurotoxicity in rats: targeting PPARgamma and HDAC pathways." Neurotox Res 26(2): 130-151.Misztak, P., P. Panczyszyn-Trzewik and M. Sowa-Kucma (2018). "Histone deacetylases (HDACs) as therapeutic target for depressive disorders." Pharmacol Rep 70(2): 398-408.Mousavi, S. E., P. Saberi, N. Ghasemkhani, N. Fakhraei, R. Mokhtari and A. R. Dehpour (2018). "Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide." J Pharm Pharm Sci 21(1): 184-194.Nanjan, M. J., M. Mohammed, B. R. Prashantha Kumar and M. J. N. Chandrasekar (2018). "Thiazolidinediones as antidiabetic agents: A critical review." Bioorg Chem 77: 548-567.Ormerod, B. K., S. J. Hanft, A. Asokan, U. Haditsch, S. W. Lee and T. D. Palmer (2013). "PPARgamma activation prevents impairments in spatial memory and neurogenesis following transient illness." Brain Behav Immun 29: 28-38.Patel, M. (2016). "Targeting Oxidative Stress in Central Nervous System Disorders." Trends Pharmacol Sci 37(9): 768-778.Patel, T. K., V. B. Patel and D. G. Rana (2017). "Possible anti-depressant effect of efavirenz and pro-depressive-like effect of voriconazole in specified doses in various experimental models of depression in mice." Pharmacol Rep 69(5): 1082-1087.Porsolt, R. D., A. Bertin and M. Jalfre (1977). "Behavioral despair in mice: a primary screening test for antidepressants." Arch Int Pharmacodyn Ther 229(2): 327-336.Rattiner, L. M., M. Davis, C. T. French and K. J. Ressler (2004). "Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in amygdala-dependent fear conditioning." J Neurosci 24(20): 4796-4806.Ren, Z., P. Yan, L. Zhu, H. Yang, Y. Zhao, B. P. Kirby, J. L. Waddington and X. Zhen (2018). "Dihydromyricetin exerts a rapid antidepressant-like effect in association with enhancement of BDNF expression and inhibition of neuroinflammation." Psychopharmacology (Berl) 235(1): 233-244.Revel, F., T. Gilbert, S. Roche, J. Drai, E. Blond, R. Ecochard and M. Bonnefoy (2015). "Influence of oxidative stress biomarkers on cognitive decline." J Alzheimers Dis 45(2): 553-560.Sayan-Ozacmak, H., V. H. Ozacmak, F. Barut and E. Jakubowska-Dogru (2012). "Rosiglitazone treatment reduces hippocampal neuronal damage possibly through alleviating oxidative stress in chronic cerebral hypoperfusion." Neurochem Int 61(3): 287-290.Shimizu, E., K. Hashimoto, N. Okamura, K. Koike, N. Komatsu, C. Kumakiri, M. Nakazato, H. Watanabe, N. Shinoda, S. Okada and M. Iyo (2003). "Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants." Biol Psychiatry 54(1): 70-75.Souza, L. C., C. B. Filho, L. D. Fabbro, M. G. de Gomes, A. T. Goes and C. R. Jesse (2013). "Depressive-like behaviour induced by an intracerebroventricular injection of streptozotocin in mice: the protective effect of fluoxetine, antitumour necrosis factor-alpha and thalidomide therapies." Behav Pharmacol 24(2): 79-86.Steru, L., R. Chermat, B. Thierry and P. Simon (1985). "The tail suspension test: a new method for screening antidepressants in mice." Psychopharmacology (Berl) 85(3): 367-370.Taciak, P. P., N. Lysenko and A. P. Mazurek (2017). "Drugs which influence serotonin transporter and serotonergic receptors: Pharmacological and clinical properties in the treatment of depression." Pharmacol Rep 70(1): 37-46.Taniguti, E. H., Y. S. Ferreira, I. J. V. Stupp, E. B. Fraga-Junior, C. B. Mendonca, F. L. Rossi, H. N. Ynoue, D. L. Doneda, L. Lopes, E. Lima, Z. S. Buss and S. Vandresen-Filho (2018). "Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice." Physiol Behav.Thabit, S. and N. S. E. El Sayed (2018). "Effect of pioglitazone and simvastatin in lipopolysaccharide-induced amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic pathway and oxidative stress." Behav Pharmacol.Tuglu, C., S. H. Kara, O. Caliyurt, E. Vardar and E. Abay (2003). "Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder." Psychopharmacology (Berl) 170(4): 429-433.Vandresen-Filho, S., L. M. Franca, J. Alcantara-Junior, L. C. Nogueira, T. M. de Brito, L. Lopes, F. M. Junior, M. L. Vanzeler, D. B. Bertoldo, P. G. Dias, A. R. Colla, A. Hoeller, M. Duzzioni, A. L. Rodrigues, T. C. de Lima, C. I. Tasca and G. G. Viola (2015). "Statins enhance cognitive performance in object location test in albino Swiss mice: involvement of beta-adrenoceptors." Physiol Behav 143: 27-34.Vandresen-Filho, S., W. C. Martins, D. B. Bertoldo, G. Mancini, A. F. De Bem and C. I. Tasca (2015). "Cerebral cortex, hippocampus, striatum and cerebellum show differential susceptibility to quinolinic acid-induced oxidative stress." Neurol Sci 36(8): 1449-1456.Willner, P., J. Scheel-Kruger and C. Belzung (2013). "The neurobiology of depression and antidepressant action." Neurosci Biobehav Rev 37(10 Pt 1): 2331-2371.Xu, S., Q. Guan, C. Wang, X. Wei, X. Chen, B. Zheng, P. An, J. Zhang, L. Chang, W. Zhou, I. Mody and Q. Wang (2014). "Rosiglitazone prevents the memory deficits induced by amyloid-beta oligomers via inhibition of inflammatory responses." Neurosci Lett 578: 7-11.Yamawaki, Y., N. Yoshioka, K. Nozaki, H. Ito, K. Oda, K. Harada, S. Shirawachi, S. Asano, H. Aizawa, S. Yamawaki, T. Kanematsu and H. Akagi (2018). "Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice." Brain Res 1680: 13-38.Yao, J., K. Zheng and X. Zhang (2015). "Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury." Mol Med Rep 12(5): 6591-6597.Yu, X., X. G. Shao, H. Sun, Y. N. Li, J. Yang, Y. C. Deng and Y. G. Huang (2008). "Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus." Brain Res 1200: 146-158.Zhang, J. C., J. Wu, Y. Fujita, W. Yao, Q. Ren, C. Yang, S. X. Li, Y. Shirayama and K. Hashimoto (2014). "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation." Int J Neuropsychopharmacol 18(4).Zhao, Q., X. Wu, S. Yan, X. Xie, Y. Fan, J. Zhang, C. Peng and Z. You (2016). "The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARgamma-mediated alteration of microglial activation phenotypes." J Neuroinflammation 13(1): 259.Zhao, Z., L. Zhang, X. D. Guo, L. L. Cao, T. F. Xue, X. J. Zhao, D. D. Yang, J. Yang, J. Ji, J. Y. Huang and X. L. Sun (2017). "Rosiglitazone Exerts an Anti-depressive Effect in Unpredictable Chronic Mild-Stress-Induced Depressive Mice by Maintaining Essential Neuron Autophagy and Inhibiting Excessive Astrocytic Apoptosis." Front Mol Neurosci 10: 293.Zhu, L., C. Nang, F. Luo, H. Pan, K. Zhang, J. Liu, R. Zhou, J. Gao, X. Chang, H. He, Y. Qiu, J. Wang, H. Long, Y. Liu and T. Yan (2016). "Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice." Physiol Behav 163: 184-192.Zong, J., X. Liao, B. Ren and Z. Wang (2018). "The antidepressant effects of rosiglitazone on rats with depression induced by neuropathic pain." Life Sci 203: 315-322.