Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-36103947

RESUMO

Methylglyoxal (MGO) is a reactive dicarbonyl compound formed as a byproduct of glycolysis. MGO is a major cell-permeant precursor of advanced glycation end products (AGEs), since it readily reacts with basic phospholipids and nucleotides, as well as amino acid residues of proteins, such as arginine, cysteine, and lysine. The AGEs production induced by MGO are widely associated with several pathologies, including neurodegenerative diseases. However, the impact of MGO metabolism and AGEs formation in the central nervous system (particularly in neurons, astrocytes and oligodendrocytes) on behavior and psychiatric diseases is not fully understood. Here, we briefly present background information on the biological activity of MGO in the central nervous system. It was gathered the available information on the role of MGO metabolism at the physiological processes, as well as at the neurobiology of psychiatry diseases, especially pain-related experiences, anxiety, depression, and cognition impairment-associated diseases. To clarify the role of MGO on behavior and associated diseases, we reviewed primarily the main findings at preclinical studies focusing on genetic and pharmacological approaches. Since monoamine neurotransmitter systems are implicated as pivotal targets on the pathophysiology and treatment of psychiatry and cognitive-related diseases, we also reviewed how MGO affects these neurotransmission systems and the implications of this phenomenon for nociception and pain; learning and cognition; and mood. In summary, this review highlights the pivotal role of glyoxalase 1 (Glo1) and MGO levels in modulating behavioral phenotypes, as well as related cellular and molecular signaling. Conclusively, this review signals dopamine as a new neurochemical MGO target, as well as highlights how MGO metabolism can modulate the pathophysiology and treatment of pain, psychiatric and cognitive-related diseases.


Assuntos
Transtornos Mentais , Aldeído Pirúvico , Humanos , Aldeído Pirúvico/farmacologia , Aldeído Pirúvico/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Cisteína , Dopamina , Lisina , Óxido de Magnésio , Dor , Arginina , Nucleotídeos
2.
Metab Brain Dis ; 37(5): 1597-1608, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35435610

RESUMO

Cholecalciferol deficiency has been associated with stress-related psychiatric disorders, particularly depression. Therefore, the present study investigated the antidepressant-like effect of cholecalciferol in female mice and the possible role of the serotonergic system in this response. The ability of cholecalciferol to elicit an antidepressant-like effect and to modulate serotonin levels in the hippocampus and prefrontal cortex of mice subjected to chronic unpredictable stress (CUS) was also investigated. The administration of cholecalciferol (2.5, 7.5, and 25 µg/kg, p.o.) for 7 days, similar to fluoxetine (10 mg/kg, p.o., serotonin reuptake inhibitor), reduced the immobility time in the tail suspension test, without altering the locomotor performance in the open-field test. Moreover, the administration of p-chlorophenylalanine methyl ester (PCPA - 100 mg/kg, i.p., for 4 days, a selective inhibitor of tryptophan hydroxylase, involved in the serotonin synthesis) abolished the antidepressant-like effect of cholecalciferol and fluoxetine in the tail suspension test, demonstrating the involvement of serotonergic system. Additionally, CUS protocol (21 days) induced depressive-like behavior in the tail suspension test and decreased serotonin levels in the prefrontal cortex and hippocampus of mice. Conversely, the administration of cholecalciferol and fluoxetine in the last 7 days of CUS protocol completely abolished the stress-induced depressive-like phenotype. Cholecalciferol was also effective to abrogate CUS-induced reduction on serotonin levels in the prefrontal cortex, but not in the hippocampus. Our results indicate that cholecalciferol has an antidepressant-like effect in mice by modulating the serotonergic system and support the assumption that cholecalciferol may have beneficial effects for the management of depression.


Assuntos
Fluoxetina , Serotonina , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Depressão/tratamento farmacológico , Feminino , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Elevação dos Membros Posteriores/psicologia , Humanos , Camundongos , Transmissão Sináptica
3.
Mol Neurobiol ; 58(2): 735-749, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33011857

RESUMO

Methylglyoxal (MGO) is an endogenous toxin, mainly produced as a by-product of glycolysis that has been associated to aging, Alzheimer's disease, and inflammation. Cell culture studies reported that MGO could impair the glyoxalase, thioredoxin, and glutathione systems. Thus, we investigated the effect of in vivo MGO administration on these systems, but no major changes were observed in the glyoxalase, thioredoxin, and glutathione systems, as evaluated in the prefrontal cortex and the hippocampus of mice. A previous study from our group indicated that MGO administration produced learning/memory deficits and depression-like behavior. Confirming these findings, the tail suspension test indicated that MGO treatment for 7 days leads to depression-like behavior in three different mice strains. MGO treatment for 12 days induced working memory impairment, as evaluated in the Y maze spontaneous alternation test, which was paralleled by low dopamine and serotonin levels in the cerebral cortex. Increased DARPP32 Thr75/Thr34 phosphorylation ratio was observed, suggesting a suppression of phosphatase 1 inhibition, which may be involved in behavioral responses to MGO. Co-treatment with a dopamine/noradrenaline reuptake inhibitor (bupropion, 10 mg/kg, p.o.) reversed the depression-like behavior and working memory impairment and restored the serotonin and dopamine levels in the cerebral cortex. Overall, the cerebral cortex monoaminergic system appears to be a preferential target of MGO toxicity, a new potential therapeutic target that remains to be addressed.


Assuntos
Depressão/fisiopatologia , Inibidores da Captação de Dopamina/farmacologia , Dopamina/deficiência , Memória de Curto Prazo , Norepinefrina/metabolismo , Aldeído Pirúvico/efeitos adversos , Animais , Bupropiona/farmacologia , Dopamina/metabolismo , Feminino , Glutationa/metabolismo , Imobilização , Memória de Curto Prazo/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Aldeído Pirúvico/administração & dosagem , Serotonina/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA