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1.
Mol Nutr Food Res ; 62(7): e1701070, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29453804

RESUMO

SCOPE: Probiotics may influence one-carbon (C1) metabolism, neurotransmitters, liver function markers, or behavior. METHODS AND RESULTS: Male adult Flinders Sensitive Line rats (model of depression, FSL; n = 22) received Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (109 or 1010 colony-forming units per day) or vehicle for 10 weeks. The controls, Flinders Resistant Line rats (FRL, n = 8), only received vehicle. C1-related metabolites were measured in plasma, urine, and different tissues. Monoamine concentrations were measured in plasma, hippocampus, and prefrontal cortex. Vehicle-treated FSL rats had higher plasma concentrations of betaine, choline, and dimethylglycine, but lower plasma homocysteine and liver S-adenosylmethionine (SAM) than FRLs. FSL rats receiving high-dose probiotics had lower plasma betaine and higher liver SAM compared to vehicle-treated FSL rats. FSLs had higher concentrations of norepinephrine, dopamine, and serotonin than FRLs across various brain regions. Probiotics decreased plasma dopamine in FSLs in a dose-dependent manner. There were no detectable changes in liver function markers or behavior. CONCLUSIONS: Probiotics reduced the flow of methyl groups via betaine, increased liver SAM, and decreased plasma dopamine and norepinephrine. Since these changes in methylation and catecholamine pathways are known to be involved in several diseases, future investigation of the effect of probiotics is warranted.


Assuntos
Antidepressivos/uso terapêutico , Bifidobacterium longum/crescimento & desenvolvimento , Depressão/terapia , Hipocampo/metabolismo , Lactobacillus helveticus/crescimento & desenvolvimento , Córtex Pré-Frontal/metabolismo , Probióticos/uso terapêutico , Animais , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Comportamento Animal , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Depressão/sangue , Depressão/metabolismo , Depressão/urina , Dopamina/sangue , Dopamina/metabolismo , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/efeitos adversos , Antagonistas de Dopamina/uso terapêutico , Liofilização , Homocisteína/antagonistas & inibidores , Homocisteína/sangue , Fígado/metabolismo , Masculino , Metilação , Neurônios/metabolismo , Norepinefrina/antagonistas & inibidores , Norepinefrina/sangue , Norepinefrina/metabolismo , Probióticos/administração & dosagem , Probióticos/efeitos adversos , Distribuição Aleatória , Ratos Mutantes , S-Adenosilmetionina/antagonistas & inibidores , S-Adenosilmetionina/metabolismo
2.
Int J Mol Sci ; 16(7): 15150-71, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-26151848

RESUMO

Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10), interferon γ-inducible protein 10 (IP-10/CXCL10), lymphotactin, macrophage inhibitory protein 3ß (MIP-3ß/CCL19), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon γ (IFN-γ)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3-hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid). Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism.


Assuntos
Comportamento Animal , Vasculite Associada ao Lúpus do Sistema Nervoso Central/metabolismo , Animais , Córtex Cerebral/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Hipocampo/metabolismo , Cinurenina/metabolismo , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/fisiopatologia , Memória , Camundongos , Camundongos Endogâmicos C57BL
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