Doxycycline reverses cognitive impairment, neuroinflammation and oxidative imbalance induced by D-amphetamine mania model in mice: A promising drug repurposing for bipolar disorder treatment?

dc.creatorChaves Filho, Adriano José Maia
dc.creatorCunha, Natássia Lopes
dc.creatorRodrigues, Patrícia de Araújo
dc.creatorSouza, Alana Gomes de
dc.creatorSoares, Michele Verde-Ramo
dc.creatorJucá, Paloma Marinho
dc.creatorQueiroz, Tatiana de
dc.creatorClemente, Dino César da Silva
dc.creatorMottin, Melina
dc.creatorAndrade, Carolina Horta
dc.creatorPeixoto, Christina Alves
dc.creatorMacedo, Danielle S.
dc.date2022-02-18T14:32:02Z
dc.date2022-02-18T14:32:02Z
dc.date2021
dc.date.accessioned2023-09-27T00:14:51Z
dc.date.available2023-09-27T00:14:51Z
dc.identifierCHAVES FILHO, Adriano José Maia; CUNHA, Natássia Lopes; RODRIGUES, Patrícia de Araújo; SOUZA, Alana Gomes de; SOARES, Michele Verde-Ramo; JUCÁ, Paloma Marinho; QUEIROZ, Tatiana de; CLEMENTE, Dino César da Silva; MOTTIN, Melina; ANDRADE, Carolina Horta. et al. Doxycycline reverses cognitive impairment, neuroinflammation and oxidative imbalance induced by D-amphetamine mania model in mice: a promising drug repurposing for bipolar disorder treatment?. European Neuropsychopharmacology, [S.L.], v. 42, p. 57-74, jan. 2021. Elsevier BV. http://dx.doi.org/10.1016/j.euroneuro.2020.11.007.
dc.identifier1873-7862
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/51291
dc.identifier10.1016/j.euroneuro.2020.11.007
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898924
dc.descriptionImmune-inflammatory mechanisms are involved in the pathophysiology of bipolar disorder. Tetracyclines present neuroprotective actions based on their anti-inflammatory and microglia suppressant effects. Doxycycline (DOXY) is a tetracycline that demonstrates a better usage profile with protective actions against inflammation and CNS injury. Here, we investigated the effects of DOXY against behavioral, neuroinflammatory, and pro-oxidative changes induced by the d-amphetamine mania model. Adult mice were given d-amphetamine 2.0 mg/kg or saline for 14 days. Between days 8 and 14, received lithium, DOXY (25 or 50 mg/kg), or their combination (lithium+DOXY) on both doses. We collected the brain areas prefrontal cortex (PFC), hippocampus, and amygdala to evaluate inflammatory and oxidative alterations. D-amphetamine induced hyperlocomotion and impairment in recognition and working memory. Lithium reversed hyperlocomotion but could not restore cognitive alterations. DOXY alone (at both doses) or combined with lithium reversed d-amphetamine-induced cognitive changes. DOXY, better than lithium, reversed the d-amphetamine-induced rise in TNFα, MPO, and lipid peroxidation. DOXY reduced the hippocampal expression of Iba1 (a marker of microglial activation), inducible nitric oxide synthase (iNOS), and nitrite. Combined with lithium, DOXY increased the phosphorylated (inactivated) form of GSK3β (Ser9). Therefore, DOXY alone or combined with lithium reversed cognitive impairment and neuroinflammation induced by the mice's d-amphetamine model. This study points to DOXY as a promising adjunctive tool for bipolar disorder treatment focused on cognition and neuroimmune changes. Our data provide the first rationale for clinical trials investigating DOXY therapeutic actions in bipolar disorder mania.
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.rightsrestricted access
dc.subjectBipolar disorder
dc.subjectDrug therapy
dc.subjectCognitive Dysfunction
dc.subjectAnimals
dc.subjectCognitive impairment
dc.subjectD-amphetamine
dc.subjectDextroamphetamine
dc.subjectDisease Models, Animal
dc.subjectDoxycycline
dc.subjectDrug Repositioning
dc.subjectMania
dc.subjectMice
dc.subjectNeuroinflammatory Diseases
dc.subjectOxidative Stress
dc.subjectBipolar disorder
dc.subjectMania
dc.subjectDoxycycline
dc.subjectD-amphetamine
dc.subjectCognitive impairment
dc.subjectNeuroinflammation
dc.subjectMicroglial activation
dc.subjectOxidative stress
dc.titleDoxycycline reverses cognitive impairment, neuroinflammation and oxidative imbalance induced by D-amphetamine mania model in mice: A promising drug repurposing for bipolar disorder treatment?
dc.typeArticle


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