Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study / Terapia celular no tratamento do transtorno bipolar: estudo piloto em um modelo animal de mania

Abstract Introduction The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). Methods Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p<0.001). In contrast, the administration of MSCs did not change hyperlocomotion, indicating no effects of this treatment on LDX-treated rats (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

Resumo Introdução Células-tronco mesenquimais (CTMs) têm emergido como um promissor tratamento em diversas doenças neurodegenerativas devido a sua plasticidade e capacidade de regenerar tecidos. Estudos pré-clínicos, clínicos e de neuroimagem têm demonstrado a presença de atrofia hipocampal no transtorno bipolar (TB). Portanto, o desenvolvimento de tratamentos capazes de regenerar tecido lesado e estimular a neurogênese poderia ser útil. Objetivos Investigar mudanças comportamentais e neuroquímicas induzidas pelo transplante de CTMs no hipocampo de ratos em um modelo animal de mania induzido por dimesilato de lisdexanfetamina (LDX). Métodos Ratos Wistar (n=65) receberam LDX (10 mg/kg) ou solução salina por via oral durante 14 dias. No oitavo dia, os animais foram transplantados com injeção de CTMs ou solução salina (1 µL contendo 25.000 células) ou lítio (47,5 mg/kg) como controle interno do experimento. Duas horas após a última dose, foram realizadas análises comportamentais e neuroquímicas. Resultados Animais que receberam LDX tiveram um aumento da atividade locomotora comparados ao grupo que recebeu solução salina (p=0,004); já o lítio reverteu a hiperatividade locomotora desses animais (p<0,001). Os animais que receberam CTMs não apresentaram alterações no comportamento, indicando ausência de efeitos sobre hiperatividade locomotora. Os níveis de BDNF hipocampais não diferiram entre os grupos (p>0.05). Conclusão Não foi possível demonstrar efeitos neuroprotetores das CTMs, administradas em dose única, em um modelo animal de mania induzido por LDX. No entanto, não se pode descartar os possíveis efeitos terapêuticos das CTMs. Mais estudos são necessários para determinar os efeitos das CTMs em estruturas cerebrais e outros alvos fisiopatológicos relacionados ao TB.

Germination and growth inhibitory effects of Hypericum myrianthum and H. polyanthemum extracts on Lactuca sativa L.

Germination and growth inhibitory effects of ethanolic crude extracts of Hypericum myrianthum and H. polyanthemum aerial parts on lettuce (Lactuca sativa) were investigated. The germination was retarded in all the tested concentrations. After seven days the final germination percentage of the most concentrated extracts was significantly reduced by both extracts in comparison with the control. The radicles length was significantly affected showing necrosis. Both species present phenolic compounds as the main components and they could be responsible for the inhibition of the germination and growth of Lactuca sativa.

Neste trabalho foi investigado o efeito inibitório de extratos etanólicos de partes aéreas de Hypericum myrianthum e Hypericum polyanthemum sobre a germinação e o crescimento de alface (Lactuca sativa). A germinação das sementes foi reduzida em todas as concentrações avaliadas. Após sete dias, o percentual de germinação foi significativamente retardado pelos extratos de ambas as plantas, nas maiores concentrações, em comparação com o grupo controle. O comprimento das radículas foi significativamente afetado, estas apresentando alguns sinais de necrose. As duas espécies apresentam compostos fenólicos como constituintes principais, os quais podem ser responsáveis pela inibição da germinação e crescimento de Lactuca sativa.