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1.
Chem Biol Interact ; 328: 109193, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32668205

RESUMO

Embryonic studies have demonstrated the neurotoxic, teratogenic, and neurobehavioral toxicity of ethanol (EtOH). Although multiple mechanisms may contribute to these effects, oxidative stress has been described as the major damage pathway. In this regard, natural antioxidants have the potential to counteract oxidative stress-induced cellular damage. Therefore, the present study aimed to investigate the potential protective role of 24-epibrassinolide (24-EPI), a natural brassinosteroid with proved antioxidant properties, in EtOH-induced teratogenic effects during early zebrafish development. Embryos (~2 h post-fertilization - hpf) were exposed to 1 % EtOH, co-exposed to 24-EPI (0.01, 0.1 and 1 µM) and to 24-EPI alone (1 µM) for 24 h. Following exposure, biochemical evaluations were made at 26 hpf, developmental analysis was made throughout the embryo-larval period, and behavioural responses were evaluated at 120 hpf. Exposure to 1 % EtOH caused an increase in the number of malformations, which were diminished by 24-EPI. In addition, EtOH induced an accumulation of GSSG and consequent reduction of GSH:GSSG ratio, indicating the involvement of oxidative mechanisms in the EtOH-induced effects. These were reverted by 24-EPI as proved by the GSSG levels and GSH:GSSG ratio that returned to control values. Furthermore, exposure to EtOH resulted in behavioural deficits at 120 hpf as observed by the disrupted response to an aversive stimulus, suggesting the involvement of neurotoxic mechanisms. 24-EPI restored the behavioural deficits observed in a dose-dependent manner. The absence of effects in the embryos exposed solely to 24-EPI showed its safety during the exposure period. In conclusion, EtOH caused developmental teratogenicity and behavioural toxicity by inducing glutathione changes, which were prevented by 24-EPI.


Assuntos
Comportamento Animal , Brassinosteroides/farmacologia , Embrião não Mamífero/patologia , Etanol/toxicidade , Substâncias Protetoras/farmacologia , Esteroides Heterocíclicos/farmacologia , Teratogênese/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Glutationa/metabolismo , Larva/efeitos dos fármacos , Comportamento Social
2.
Nature ; 583(7816): 415-420, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555456

RESUMO

Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts2,3. However, the mechanistic basis of this microbiota-brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine ß-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.


Assuntos
Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/fisiologia , Intestinos/microbiologia , Neurotransmissores/metabolismo , Providencia/metabolismo , Olfato/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Microbioma Gastrointestinal/fisiologia , Metabolômica , Mutação , Octanóis/farmacologia , Octopamina/biossíntese , Octopamina/metabolismo , Providencia/enzimologia , Providencia/fisiologia , Receptores de Amina Biogênica/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Células Receptoras Sensoriais/metabolismo , Olfato/efeitos dos fármacos , Tiramina/biossíntese , Tiramina/metabolismo
3.
J Neurosci ; 40(23): 4551-4564, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32350040

RESUMO

Forming effective responses to threatening stimuli requires the adequate and coordinated emergence of stress-related internal states. Such ability depends on early-life experiences and, in connection, the adequate formation of neuromodulatory systems, particularly serotonergic signaling. Here, we assess the serotonergic background of experience-dependent behavioral responsiveness using male and female zebrafish (Danio rerio). For the first time, we have characterized a period during behavioral metamorphosis in which zebrafish are highly reactive to their environment. Absence of social stimuli during this phase established by isolated rearing fundamentally altered the behavioral phenotype of postmetamorphic zebrafish in a challenge-specific manner, partially due to reduced responsiveness and an inability to develop stress-associated arousal state. In line with this, isolation differentially affected whole-brain serotonergic signaling in resting and stress-induced conditions, an effect that was localized in the dorsal pallium and was negatively associated with responsiveness. Administration of the serotonin receptor 1A partial agonist buspirone prevented the isolation-induced serotonin response to novelty in the level of the whole brain and the forebrain as well, without affecting catecholamine levels, and rescued stress-induced arousal along with challenge-induced behaviors, which together indicates functional connection between these changes. In summary, there is a consistent negative association between behavioral responsiveness and serotonergic signaling in zebrafish, which is well recognizable through the modifying effects of developmental perturbation and pharmacological manipulations as well. Our results imply a conserved serotonergic mechanism that context-dependently modulates environmental reactivity and is highly sensitive to experiences acquired during a specific early-life time window, a phenomenon that was previously only suggested in mammals.SIGNIFICANCE STATEMENT The ability to respond to challenges is a fundamental factor in survival. We show that zebrafish that lack appropriate social stimuli in a sensitive developmental period show exacerbated alertness in nonstressful conditions while failing to react adequately to stressors. This shift is reflected inversely by central serotonergic signaling, a system that is implicated in numerous mental disorders in humans. Serotonergic changes in brain regions modulating responsivity and behavioral impairment were both prevented by the pharmacological blockade of serotonergic function. These results imply a serotonergic mechanism in zebrafish that transmits early-life experiences to the later phenotype by shaping stress-dependent behavioral reactivity, a phenomenon that was previously only suggested in mammals. Zebrafish provide new insights into early-life-dependent neuromodulation of behavioral stress-responses.


Assuntos
Nível de Alerta/fisiologia , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Receptor 5-HT1A de Serotonina/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/fisiologia , Animais , Nível de Alerta/efeitos dos fármacos , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Feminino , Masculino , Isolamento Social/psicologia , Peixe-Zebra
4.
Life Sci ; 253: 117703, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32334010

RESUMO

AIMS: Vitamin D is a well-known endocrine regulator of calcium/phosphate homeostasis and has been reported as having a wide range of activities that are potentially beneficial for human health. This study aimed to investigate the effects of pretreatment of vitamin D3 (100, 1000, and 10,000 IU/kg) against lipopolysaccharide (LPS)-induced cognitive impairment in rats. MAIN METHODS: Male Wistar rats were divided into five groups. The passive avoidance test and Morris water maze (MWM) test were conducted to evaluate the learning and memory function. Oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), total thiol content as well as interleukin (IL)-6 were evaluated in the hippocampus tissue. KEY FINDINGS: The intraperitoneal (i.p.) injection of LPS (1 mg/kg) correlates with deficits in passive avoidance and spatial learning in the systemic inflammation model. However, pretreatment with vitamin D3 improved LPS-induced cognitive impairment. In addition, vitamin D3 decreased IL-6 and MDA levels, whereas the activities of CAT, SOD, and total thiol content in the hippocampus tissue were significantly increased. SIGNIFICANCE: In conclusion, our results suggest that vitamin D3 plays a protective role against memory dysfunction caused by LPS-induced inflammation through inhibition of oxidative stress and inflammation in the hippocampus. Vitamin D may be a promising potential therapeutic supplement for the treatment or prevention of learning and memory disorders.


Assuntos
Colecalciferol/farmacologia , Disfunção Cognitiva/prevenção & controle , Inflamação/prevenção & controle , Transtornos da Memória/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Colecalciferol/administração & dosagem , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Lipopolissacarídeos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar
5.
Bull Environ Contam Toxicol ; 104(4): 477-483, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32193572

RESUMO

The application of nano-level passivating agents in the remediation of soil heavy metal pollution has received widespread attention, but its harm to soil animals should also be addressed. This study explored the effect of three nanomaterials-nanohydroxyapatite apatite (n-HAP), nano zeolite (n-zeolite), and nanometer iron oxide (n-Fe3O4), on catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content through filter paper contact test. The effects of nanomaterials spiked at 1.5%wt of soils on earthworm avoidance behavior were also be studied, and the crystallinity and surface charge of three nanomaterials were characterized. The results showed that the activities of CAT, SOD and POD and the content of MDA have been changed at different level. And earthworms have obvious avoidance behavior to the three kinds of nanomaterials. Therefore, nanomaterials do have adverse effects on earthworms, and their biological toxicity should be considered when selecting passivating agents for soil heavy metal pollution remediation.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Recuperação e Remediação Ambiental/métodos , Reação de Fuga/efeitos dos fármacos , Nanoestruturas/toxicidade , Oligoquetos/efeitos dos fármacos , Poluentes do Solo/toxicidade , Solo/química , Animais , Catalase/metabolismo , Malondialdeído/metabolismo , Nanoestruturas/química , Oligoquetos/metabolismo , Peroxidase/metabolismo , Poluentes do Solo/química , Superóxido Dismutase/metabolismo
6.
Bull Environ Contam Toxicol ; 104(5): 588-594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32193571

RESUMO

Female vinegar flies (Drosophila melanogaster) preferentially oviposit eggs on oviposition substrates that decrease larval foraging costs. We tested whether female D. melanogaster would avoid oviposition substrates containing lead (Pb2+), which could potentially decrease offspring fitness. Wild type D. melanogaster were reared on control or Pb-treated medium from egg stage to adulthood and tested for differences in oviposition substrate preference, fecundity (number of eggs laid) and Pb accumulation. Control females laid a significantly lower proportion of eggs on Pb-treated substrates than Pb-treated females. Pb-treated females laid significantly more eggs than control females. Pb-treated adults accumulated significantly more Pb than control-treated adults. These results indicate that Pb exposure disrupts normal oviposition avoidance behaviors, which could increase larval foraging costs for larval offspring. These factors could induce population declines and have cascading implications for the ecosystem.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Drosophila melanogaster/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Larva/efeitos dos fármacos , Chumbo/toxicidade , Oviposição/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/fisiologia , Ecossistema , Feminino , Fertilidade/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Modelos Teóricos
7.
Proc Natl Acad Sci U S A ; 117(14): 8104-8114, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32193346

RESUMO

There is extensive evidence that glucocorticoid hormones enhance memory consolidation, helping to ensure that emotionally significant events are well remembered. Prior findings suggest that the anteroventral region of bed nuclei of the stria terminalis (avBST) regulates glucocorticoid release, suggesting the potential for avBST activity to influence memory consolidation following an emotionally arousing learning event. To investigate this issue, male Sprague-Dawley rats underwent inhibitory avoidance training and repeated measurement of stress hormones, immediately followed by optogenetic manipulations of either the avBST or its projections to downstream regions, and 48 h later were tested for retention. The results indicate that avBST inhibition augmented posttraining pituitary-adrenal output and enhanced the memory for inhibitory avoidance training. Pretreatment with a glucocorticoid synthesis inhibitor blocked the memory enhancement as well as the potentiated corticosterone response, indicating the dependence of the memory enhancement on glucocorticoid release during the immediate posttraining period. In contrast, posttraining avBST stimulation decreased retention yet had no effect on stress hormonal output. Subsequent experiments revealed that inhibition of avBST input to the paraventricular hypothalamus enhanced stress hormonal output and subsequent retention, whereas stimulation did not affect either. Conversely, stimulation-but not inhibition-of avBST input to the ventrolateral periaqueductal gray impaired consolidation, whereas neither manipulation affected glucocorticoid secretion. These findings indicate that divergent pathways from the avBST are responsible for the mnemonic effects of avBST inhibition versus stimulation and do so via glucocorticoid-dependent and -independent mechanisms, respectively.


Assuntos
Aprendizagem da Esquiva/fisiologia , Glucocorticoides/metabolismo , Consolidação da Memória/fisiologia , Núcleos Septais/fisiologia , Hormônio Adrenocorticotrópico/análise , Hormônio Adrenocorticotrópico/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Corticosterona/análise , Corticosterona/metabolismo , Glucocorticoides/análise , Glucocorticoides/antagonistas & inibidores , Masculino , Consolidação da Memória/efeitos dos fármacos , Metirapona/administração & dosagem , Modelos Animais , Vias Neurais/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Optogenética , Núcleo Hipotalâmico Paraventricular/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/metabolismo , Núcleos Septais/citologia
8.
Toxicol Appl Pharmacol ; 394: 114954, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171570

RESUMO

Learning and memory deficits are obvious symptoms that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin-angiotensin system (RAS) is directly associated with ß-cell dysfunction and diabetic complications, including cognitive impairment. Here, we investigated the protective and molecular effects of two RAS modifiers, aliskiren; renin inhibitor and captopril; angiotensin converting enzyme inhibitor, on cognitive deficits in the rat hippocampus. Injection of low dose streptozotocin for 4 days resulted in type 1 diabetes. Then, poorly controlled diabetes was mimicked with ineffective daily doses of insulin for 4 weeks. The hyperglycaemia and pancreatic atrophy caused memory disturbance that were identifiable in behavioural tests, hippocampal neurodegeneration, and the following significant changes in the hippocampus, increases in the inflammatory marker interleukin 1ß, cholinesterase, the oxidative stress marker malondialdehyde and protein expression of phosphorylated extracellular-signal-regulated kinase and glycogen synthase kinase-3 beta versus decrease in the antioxidant reduced glutathione and protein expression of phosphorylated glycogen synthase kinase-3 beta. Blocking RAS with either drugs along with insulin amended all previously mentioned parameters. Aliskiren stabilized the blood glucose level and restored normal pancreatic integrity and hippocampal malondialdehyde level. Aliskiren showed superior protection against the hippocampal degeneration displayed in the earlier behavioural modification in the passive avoidance test, and the aliskiren group outperformed the control group in the novel object recognition test. We therefore conclude that aliskiren and captopril reversed the diabetic state and cognitive deficits in rats with poorly controlled STZ-induced diabetes through reducing oxidative stress and inflammation and modulating protein expression.


Assuntos
Amidas/uso terapêutico , Captopril/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/psicologia , Diabetes Mellitus Experimental/psicologia , Fumaratos/uso terapêutico , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Hipocampo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/patologia , Colinesterases/metabolismo , Disfunção Cognitiva/etiologia , Diabetes Mellitus Experimental/patologia , Hipocampo/enzimologia , Hipocampo/patologia , Interleucina-1beta/biossíntese , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Pâncreas/patologia , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos
9.
Sci China Life Sci ; 63(9): 1-9, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32180109

RESUMO

Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens (NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein (GluA1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Dependência de Morfina/metabolismo , Morfina/efeitos adversos , Núcleo Accumbens/efeitos dos fármacos , Ondas Ultrassônicas/efeitos adversos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Estimulação Encefálica Profunda , Cinética , Masculino , Camundongos Endogâmicos C57BL , Morfina/administração & dosagem
10.
Psychopharmacology (Berl) ; 237(5): 1383-1396, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31984447

RESUMO

RATIONALE: Treatment of bipolar disorder (BPD) with lithium and olanzapine concurrent administration is a major medicine issue with the elusive neurobiological mechanisms underlying the cognitive function. OBJECTIVE: To clarify the precise mechanisms involved, the possible role of the hippocampus (HPC) and prefrontal cortical (PFC) NMDA receptors and CAMKII-CREB signaling pathway in the interactive effects of lithium and olanzapine in memory consolidation was evaluated. The dorsal hippocampal CA1 regions of adult male Wistar rats were bilaterally cannulated and a step-through inhibitory avoidance apparatus was used to assess memory consolidation. The changes in p-CAMKII/CAMKII and p-CREB/CREB ratio in the HPC and the PFC were measured by Western blot analysis. RESULTS: Post-training administration of lithium (20, 30, and 40 mg/kg, i.p.) dose-dependently decreased memory consolidation whereas post-training administration olanzapine (2 and 5 mg/kg, i.p.) increased memory consolidation. Post-training administration of certain doses of olanzapine (1, 2, and 5 mg/kg, i.p.) dose-dependently improved lithium-induced memory impairment. Post-training administration of ineffective doses of the NMDA (10-5 and 10-4 µg/rat, intra-CA1) plus an ineffective dose of olanzapine (1 mg/kg, i.p.) dose-dependently improved the lithium-induced memory impairment. Post-training microinjection of ineffective doses of the NMDA (10-5 and 10-4 µg/rat, intra-CA1) dose-dependently potentiated the memory improvement induced by olanzapine (1 mg/kg, i.p.) on lithium-induced memory impairment which was associated with the enhancement of the levels of p-CAMKII and p-CREB in the HPC and the PFC. Post-training microinjection of ineffective doses of the noncompetitive NMDA receptor antagonist, MK-801 (0.0625 and 0.0125 µg/rat, intra-CA1), dose-dependently decreased the memory improvement induced by olanzapine (5 mg/kg, i.p.) on lithium-induced memory impairment which was related to the reduced levels of HPC and PFC CAMKII-CREB. CONCLUSION: The results strongly revealed that there is a functional interaction among lithium and olanzapine through the HPC and the PFC NMDA receptor mechanism in memory consolidation which is mediated with the CAMKII-CREB signaling pathway.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Carbonato de Lítio/administração & dosagem , Consolidação da Memória/fisiologia , Olanzapina/administração & dosagem , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Consolidação da Memória/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
11.
Mol Cell Biol ; 40(6)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31932477

RESUMO

Nrf2 (NF-E2-related-factor 2) is a stress-responsive transcription factor that protects cells against oxidative stresses. To clarify whether Nrf2 prevents Alzheimer's disease (AD), AD model AppNL-G-F/NL-G-F knock-in (AppNLGF ) mice were studied in combination with genetic Nrf2 induction model Keap1FA/FA mice. While AppNLGF mice displayed shorter latency to escape than wild-type mice in the passive-avoidance task, the impairment was improved in AppNLGF ::Keap1FA/FA mice. Matrix-assisted laser desorption ionization-mass spectrometry imaging revealed that reduced glutathione levels were elevated by Nrf2 induction in AppNLGF ::Keap1FA/FA mouse brains compared to AppNLGF mouse brains. Genetic Nrf2 induction in AppNLGF mice markedly suppressed the elevation of the oxidative stress marker 8-OHdG and Iba1-positive microglial cell number. We also determined the plasmalogen-phosphatidylethanolamine (PlsPE) level as an AD biomarker. PlsPE containing polyunsaturated fatty acids was decreased in the AppNLGF mouse brain, but Nrf2 induction attenuated this decline. To evaluate whether pharmacological induction of Nrf2 elicits beneficial effects for AD treatment, we tested the natural compound 6-MSITC [6-(methylsulfinyl)hexyl isothiocyanate]. Administration of 6-MSITC improved the impaired cognition of AppNLGF mice in the passive-avoidance task. These results demonstrate that the induction of Nrf2 ameliorates cognitive impairment in the AD model mouse by suppressing oxidative stress and neuroinflammation, suggesting that Nrf2 is an important therapeutic target of AD.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/fisiologia , Peptídeos beta-Amiloides/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Proteínas de Ligação ao Cálcio/metabolismo , Cognição/efeitos dos fármacos , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Glutationa/sangue , Inflamação/patologia , Isotiocianatos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidiletanolaminas/metabolismo , Placa Amiloide/genética , Placa Amiloide/patologia , Plasmalogênios/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
12.
Chemosphere ; 245: 125679, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31869672

RESUMO

17ß-Trenbolone (17ß-TBOH) is an endocrine disruptor that has been widely reported in aquatic organisms. However, little is known about the effect of 17ß-TBOH on mammals, particularly on the development of adolescents. Through a series of behavioural experiments, exposure to at 80 µg kg -1 d -1 and 800 µg kg -1 d -1 17ß-TBOH during puberty (from PND 28 to 56, male mice) increased anxiety-like behaviours. Exposure to the low dose of 80 µg kg -1 d -1 resulted in a clear social avoidance behaviour in mice. The two doses affected testicular development and endogenous androgen synthesis in male mice. In addition, 17ß-TBOH exposure altered the differentiation of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex (mPFC). These results reveal the effects of 17ß-TBOH on the behaviours, gonadal and neurodevelopment of adolescent mammals. In addition, the inhibition of the secretion of endogenous hormones and decrease in the formation of the myelin sheath in mPFC may be associated with the 17ß-TBOH-induced behavioural changes in mice.


Assuntos
Hormônios Esteroides Gonadais/biossíntese , Comportamento Social , Acetato de Trembolona/farmacologia , Animais , Ansiedade/induzido quimicamente , Aprendizagem da Esquiva/efeitos dos fármacos , Disruptores Endócrinos/farmacologia , Masculino , Camundongos , Bainha de Mielina/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos
13.
Bratisl Lek Listy ; 120(12): 881-886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855045

RESUMO

BACKGROUND: Galangin, a flavonoid compound with acetylcholinesterase inhibitory activity, may improve cognitive functions by enhancing cholinergic transmission. OBJECTIVES: We aimed to investigate the effects of galangin on spatial memory impairment in rats. METHODS: The effects of galangin (50 and 100 mg/kg) and reference anti-dementia drug donepezil (1mg/kg) administrations were examined on memory impairment induced by the muscarinic cholinergic receptor antagonist scopolamine or the nicotinic cholinergic receptor antagonist mecamylamine in the Morris water maze (MWM) test. Hippocampal acetylcholine concentrations were also determined. RESULTS: Galangin 50 and 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in scopolamine-treated rats. Galangin 100 mg/kg significantly decreased the mean distance to platform and increased the time spent in the escape platform quadrant in mecamylamine-treated rats. The effects of galangin in the MWM were comparable with donepezil. Scopolamine and mecamylamine decreased acetylcholine concentrations, whereas galangin both alone and with mecamylamine or scopolamine administration increased acetylcholine concentrations. CONCLUSION: Galangin improved memory impairment comparable to donepezil and nicotinic and muscarinic receptors may be involved in this effect. Galangin may be considered as a promising flavonoid in the prevention and treatment of memory impairment in Alzheimer's disease and other dementias (Fig. 7,Ref. 37).


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Flavonoides/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Mecamilamina/toxicidade , Escopolamina/toxicidade , Memória Espacial/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/fisiologia , Inibidores da Colinesterase , Donepezila , Flavonoides/administração & dosagem , Aprendizagem em Labirinto/fisiologia , Mecamilamina/efeitos adversos , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Escopolamina/efeitos adversos
14.
Nutrients ; 11(12)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31756901

RESUMO

Geum japonicum, commonly known as Asian herb bennet, has been used as a diuretic, astringent, anti-dizziness, and anti-headache agent in traditional medicine. Since the antidepressant-like effects of G. japonicum extract have not been well studied, we examined the antidepressant-like effects of G. japonicum extract using depressive-like behavior induced in mice through daily injection of corticosterone (CORT). ICR mice (male, 8 weeks old) were treated with CORT (40 mg/kg, i.p.) and orally administered using oral gavage needles with G. japonicum extract (30, 100, and 300 mg/kg) for 4 weeks. Behavioral experiments were performed 1 h after administration. The control mice exhibited a significant increase in the immobility times in the tail suspension and forced swim tests as well as the step-through latency time in the passive avoidance test. Further, the control group showed a significant decrease in their sucrose consumption. However, treatment with G. japonicum extract at doses of 100 and 300 mg/kg significantly improved these depression-like behaviors without altering the locomotor activity. Moreover, treatment with G. japonicum extract significantly prevented the decrease in the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. In addition, G. japonicum extract had neuroprotective effects against CORT-induced neurotoxicity in SH-SY5Y cells. Our study indicates that G. japonicum extract exhibits antidepressant-like activity in CORT-induced depressive mice, which might be as a result of increased BDNF expression.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Corticosterona , Depressão/tratamento farmacológico , Geum , Extratos Vegetais/farmacologia , Animais , Antidepressivos/isolamento & purificação , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo , Linhagem Celular Tumoral , Depressão/induzido quimicamente , Depressão/fisiopatologia , Depressão/psicologia , Modelos Animais de Doenças , Comportamento Alimentar/efeitos dos fármacos , Geum/química , Humanos , Locomoção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Tempo de Reação/efeitos dos fármacos , Fatores de Tempo
15.
Environ Sci Pollut Res Int ; 26(36): 36615-36622, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31734837

RESUMO

Spirotetramat is a toxic commercially known as Movento used to control pistachio psylla pests. In the present study, the effects of Movento on passive avoidance learning of rats and their ability to explore the novel object in the novel object recognition test were investigated. The changes in the concentration of hippocampal brain-derived neurotrophic factor (BDNF) proteins were evaluated, too. Male Wistar rats were gavaged at different dosages of the Movento (50, 100, 250, 500, 1000, 1250, and 1500 mg/kg) or saline for 7 days (administered every 2 days). We showed that Movento caused 50 and 100% mortality at the dose of 1250 and 1500 mg/kg, respectively. At the dose of 1000 mg/kg, Movento significantly decreased locomotor activity (P < 0.05). These rats also displayed a significant decrease in the number of training trials in the shuttle box and the ability to recognize a novel object compared with the control group (P < 0.01). The BDNF protein level of hippocampus also showed a significant decrease in the Movento (1000 mg/kg) compared with the control group (P < 0.01) while the number of pancellular necrosis pyramidal CA1 cells increased significantly in the Movento group (P < 0.001). We concluded that exposure to Movento can decline sensory, motor, and learning in rats.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Compostos Aza/toxicidade , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/efeitos dos fármacos , Inseticidas/toxicidade , Compostos de Espiro/toxicidade , Animais , Compostos Aza/administração & dosagem , Hipocampo/metabolismo , Hipocampo/patologia , Inseticidas/administração & dosagem , Dose Letal Mediana , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Compostos de Espiro/administração & dosagem
16.
J Chem Ecol ; 45(10): 838-848, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31677136

RESUMO

Many aquatic organisms detect and avoid damage-released cues from conspecifics, but the chemical basis of such responses, and the effects of prolonged exposure to such cues, remain poorly understood. Injured tadpoles of the cane toad (Rhinella marina) produce chemical cues that induce avoidance by conspecific tadpoles; and chronic exposure to those cues decreases rates of tadpole survival and growth, and reduces body size at metamorphosis. Such effects suggest that we might be able to use the cane toads' alarm cue for biocontrol of invasive populations in Australia. In the present study, we examined behavioral and ecological effects of compounds that are present in cane toad tadpoles and thus, might trigger avoidance of crushed conspecifics. Four chemicals (L-Arg, L-Leu-L-Leu-OH, L-Leu-L-Ile-OH and suberic acid) induced behavioral avoidance in toad tadpoles at some (but not all) dosage levels, so we then exposed toad larvae to these chemicals over the entire period of larval development. Larval survival and size at metamorphosis were decreased by chronic exposure to crushed conspecifics (consistent with earlier studies), but not by exposure to any of the four chemicals. Indeed, L-Arg increased body size at metamorphosis. We conclude that the behavioral response to crushed conspecifics by cane toad tadpoles can be elicited by a variety of chemical cues, but that consistent exposure to these individual chemical cues does not affect tadpole viability or developmental trajectory. The optimal behavioral tactic of a tadpole may be to flee if it encounters even a single chemical cue likely to have come from an injured conspecific (indicative of predation risk), whereas the continuing presence of that single chemical (but no others) provides a less reliable signal of predation risk. Our data are consistent with results from studies on fish, that suggest a role for multiple chemicals in initiating alarm responses to damage-released cues.


Assuntos
Arginina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Bufo marinus/fisiologia , Caprilatos/farmacologia , Ácidos Dicarboxílicos/farmacologia , Oligopeptídeos/farmacologia , Animais , Tamanho Corporal/efeitos dos fármacos , Bufo marinus/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Larva/fisiologia , Metamorfose Biológica/efeitos dos fármacos , Oligopeptídeos/química
17.
Bull Environ Contam Toxicol ; 103(6): 776-782, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31686122

RESUMO

Earthworms exhibit clumping behaviour in and out of the soil. However, it remains unknown if such social behaviour ultimately influences the outcome of ecotoxicological experiments in the laboratory. We performed several overnight avoidance tests to determine whether social behaviour (i.e., local enhancement) is a factor in pollution avoidance behaviour in the earthworm Eisenia fetida. The results showed that there was no clear influence of social behaviour on the choice or avoidance of Cd contaminated soils, although we suspect that 50 mg Cd/kg might not have been high enough to elicit a significant avoidance response. Nevertheless, when offered a choice between clean undisturbed soil and previously inhabited soil, the worms preferred the previously inhabited soil (p < 0.01). While the level of metal pollution investigated in this study did not disrupt or help predict social dynamics, local enhancement, perhaps driven by some sort of habitat imprinting, was successfully documented in Eisenia fetida.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Cádmio/toxicidade , Oligoquetos/efeitos dos fármacos , Comportamento Social , Poluentes do Solo/toxicidade , Solo/química , Animais , Bioensaio , Cádmio/análise , Ecossistema , Modelos Teóricos , Oligoquetos/fisiologia , Poluentes do Solo/análise , Testes de Toxicidade
18.
Environ Toxicol Pharmacol ; 72: 103262, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31634705

RESUMO

The objective of this study was to evaluate the toxicity of the antiparasitic agent eprinomectin in two subtropical soils, using ecotoxicological lethality, reproduction and avoidance behavior tests with springtails (Folsomia candida). Eprinomectin concentrations were 0 (control), 0.5, 1, 2, 4, 8, 12, 16 and 20 mg kg-1 of dry soil combined with either Entisol or Oxisol soils. Statistically significant toxic effects of eprinomectin on springtails were observed in both soils. Eprinomectin was lethal starting at 8 mg kg-1 of dry soil in Entisol, and 20 mg kg-1 of dry soil in Oxisol, with effects less than 50% at lethal concentrations. Reductions in the reproduction rate of the springtails were also observed starting at 8 mg kg-1 of dry soil in Entisol, and 0.5 mg kg-1 of dry soil in Oxisol. ECrepr50 value calculated for Entisol was 4.38 ±â€¯0.62 mg kg-1 of dry soil; for Oxisol the ECrepr50 was above the highest tested concentration. For avoidance behavior, the effect occurred from 0.5 mg kg-1 of dry soil for both soils. In Entisol, all concentrations caused avoidance of more than 95%, and in Oxisol the ECavoi50 value was 1.33 ±â€¯0.83 mg kg-1 of dry soil. We conclude that eprinomectin affected survival, reproduction and caused avoidance behavior of F. candida in both soils. The toxic effects were greater as the concentration in the soils increased. The effects in Oxisol were less intense than those in Entisol with respect to the affected springtails. This discrepancy may be attributed to the different physicochemical characteristics of the soils that determine the retention capacity for eprinomectin; in particular, there are greater contents of clay, organic matter and cation exchange capacity in Oxisol.


Assuntos
Antiparasitários/toxicidade , Artrópodes/efeitos dos fármacos , Ivermectina/análogos & derivados , Poluentes do Solo/toxicidade , Solo/química , Animais , Artrópodes/fisiologia , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Biomarcadores , Ivermectina/toxicidade , Reprodução/efeitos dos fármacos
19.
Bull Exp Biol Med ; 167(6): 711-715, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31655990

RESUMO

We studied the involvement of protein kinase Mζ (PKMζ) in the mechanisms of amnesia development within 10 days after disruption of conditioned food aversion memory with ZIP (a PKMζ inhibitor). Repeated training performed in 3 days after amnesia induction with ZIP, led to the formation of conditioned food aversion memory, but the number of combined presentations of food and reinforcer stimuli was lower than during the initial training. Repeated training performed in 10 days after amnesia induction also led to memory formation, but the number of combined presentations of the stimuli was similar to that during the initial training. It was hypothesized that at the early stages of ZIP-induced amnesia, residual memory trace can be restored and amplified during repeated training, which led to memory expression at the behavioral level. At the late stages of amnesia, this memory trace was completely erased and repeated training led to the formation of a new memory. Thus, PKMζ inhibition results in the relatively fast impairment of memory retrieval and induces long-term process of memory erasing.


Assuntos
Amnésia/induzido quimicamente , Lipopeptídeos/farmacologia , Memória de Longo Prazo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Amnésia/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Condicionamento Psicológico/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Caracois Helix/efeitos dos fármacos , Caracois Helix/fisiologia , Consolidação da Memória/efeitos dos fármacos , Consolidação da Memória/fisiologia , Proteína Quinase C/antagonistas & inibidores , Fatores de Tempo
20.
Ecotoxicol Environ Saf ; 186: 109757, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606638

RESUMO

Contamination seems to exert a crucial role in the spatial distribution of some organisms, such as shrimps and fish. Both, especially the freshwater fish Danio rerio and the shrimp Atyaephyra desmarestii, have been tested experimentally for their avoidance response and have showed the ability to escape from toxic effects. As the behavior of avoiding or not the contamination might be altered in the presence of other factors, the aim of the current study was to verify whether the avoidance response of both species, when exposed jointly (multispecies tests), to a copper gradient is different from the avoidance response observed in monospecies tests. The avoidance was assessed in a multi-compartmented exposure system, in which a copper gradient was simulated. Organisms were tested individually and together. Both species avoided potentially toxic copper concentrations; however, shrimps were slightly more sensitive in the monospecies tests: AC50 (avoidance concentration for 50% of the population) of 60 (53-68) µg/L for the zebrafish and 50 (45-56) µg/L for the shrimp. In the multispecies tests, the sensitivity pattern changed: the avoidance response by the fish [AC50: 30 (14-46) µg/L] was greater than by the shrimps [AC50: 70 (22-141) µg/L]. Although the AC50 values are in the same order of magnitude, a slight trend to change the avoidance pattern was observed in the shrimps during multispecies test: the avoidance was lower and time-delayed. This behavioral change could be linked to the stress caused by the zebrafish sharing the space with the shrimps, perhaps increasing the territorialism of the fish, or a delay in the shrimps detecting the risk of contamination.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Cobre/toxicidade , Decápodes/fisiologia , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Relação Dose-Resposta a Droga , Água Doce/química , Especificidade da Espécie
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