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1.
Ecotoxicol Environ Saf ; 205: 111348, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979803

RESUMO

Transgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (F0) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance.


Assuntos
Cumarínicos/toxicidade , Repelentes de Insetos/toxicidade , Permetrina/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Cumarínicos/metabolismo , Ecossistema , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Metabolismo dos Lipídeos , Peixe-Zebra/metabolismo , Peixe-Zebra/fisiologia
2.
Nat Commun ; 11(1): 4634, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929078

RESUMO

The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.


Assuntos
Cromatina/metabolismo , Corpo Estriado/enzimologia , Dependência de Heroína/enzimologia , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Animais , Sequência de Bases , Comportamento Animal/efeitos dos fármacos , Sinais (Psicologia) , Genoma , Células HEK293 , Heroína/efeitos adversos , Humanos , Masculino , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-fyn/antagonistas & inibidores , Ratos Long-Evans , Autoadministração , Transcrição Genética/efeitos dos fármacos , Proteínas tau/metabolismo
3.
Ecotoxicol Environ Saf ; 205: 111289, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949839

RESUMO

The Deepwater Horizon oil spill released 3.19 million barrels of crude oil into the Gulf of Mexico, making it the largest oil spill in U.S. history. Weathering and the application of dispersants can alter the solubility of compounds within crude oil, thus modifying the acute toxicity of the crude oil to aquatic life. The primary aim of our study was to determine the lasting impact of early-life stage sheepshead minnow (Cyprinodon variegatus variegatus) exposure to weathered, unweathered and dispersed crude oil on prey capture, male aggression, novel object interaction and global DNA methylation. Embryos were exposed from 1 to 10 dpf to water accommodations of crude oil and were raised to adulthood in artificial seawater. Our results suggest exposure to crude oil did not result in lasting impairment of complex behavioral responses of male sheepshead minnow. Exposure to dispersed weathered oil, however, decreased border dwelling in response to a novel object (i.e. decreased anxiety). Principal component analysis revealed that exposure to weathered oil had no overarching effect, but that unweathered crude oil increased variability in exploratory behaviors but decreased variability in anxiety-associated behaviors. Further work is needed to understand the effects of oil exposure on fish behavior and the potential ecological impact of subtle behavioral changes in fishes.


Assuntos
Comportamento Animal/efeitos dos fármacos , Peixes Listrados/fisiologia , Larva/efeitos dos fármacos , Poluição por Petróleo/efeitos adversos , Petróleo/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Metilação de DNA/efeitos dos fármacos , Ecologia , Golfo do México , Peixes Listrados/genética , Larva/genética , Larva/fisiologia , Masculino , Água do Mar/química , Tempo (Meteorologia)
4.
PLoS One ; 15(8): e0237196, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764777

RESUMO

Current antidepressant therapy has several disadvantages related to the properties of antidepressants. Considering their unfavourable features, the process of searching for new antidepressant drugs with better safety and tolerability requires consistent efforts and many complementary studies. Serotonin 5-HT1A receptor is considered as an interesting target of antidepressant therapy. In the present study, the intrinsic activity at different signaling pathways coupled to serotonin 5-HT1A receptor, antidepressant-like and pharmacokinetic properties, and the safety profile of two novel imidazopurine-2,4-dione derivatives, namely compounds AZ-853 (8-(4-(4-(2-fluorophenyl)piperazin-1-yl)butyl)-1,3-dimethyl-1H- imidazo[2,1-f]purine-2,4(3H,8H)-dione) and AZ-861 (1,3-dimethyl-8-(4-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)butyl)-1H-imidazo[2,1-f]purine-2,4(3H,8H)-dione), were studied in animal models through in vitro and in vivo experiments. We demonstrated that AZ-853 and AZ-861, which structurally differ by one substituent and its placement in the phenyl ring, showed varied functional, pharmacological, and pharmacokinetic properties as well as side effect profiles. AZ-861 exhibited stronger agonistic action in all functional assays. After acute and repeated administration in mice, both compounds showed antidepressant-like activity in the forced swim test, which was partially mediated by 5-HT1A receptor activation. AZ-853 showed a more potent antidepressant-like effect, presumably due to its better penetration into brain structures. Both compounds did not show anticholinergic properties, but after repeated administration, they induced weak sedation and lipid metabolism disturbances without affecting serum glucose level. The stronger α1-adrenolytic effect of AZ-853 is responsible for decreased systolic blood pressure, and in contrast to AZ-861, AZ-853 induced weight gain in mice. The interesting comparative pharmacological profiles of AZ-853 and AZ-861 encourage to conduct further experiments to fully understand their mechanisms and differences in action.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Receptor 5-HT1A de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Animais , Antidepressivos/química , Técnicas de Observação do Comportamento , Comportamento Animal/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Depressão/diagnóstico , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Piperazinas/química , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Agonistas do Receptor 5-HT1 de Serotonina/química , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Relação Estrutura-Atividade , Ganho de Peso/efeitos dos fármacos
5.
PLoS One ; 15(8): e0237353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785255

RESUMO

Airborne spatial repellency (SR) is characterized and distinguished from other chemical actions including contact locomotor excitation and toxicity. The use of volatile spatial repellents is a potential new intervention class for combatting mosquito-borne pathogen transmission; therefore, continuing investigations on the actions of these chemicals that modify mosquito host-seeking behavior (i.e., bite prevention) is needed. The objective of this study is to characterize the key behavioral avoidance actions of transfluthrin (TFT) to advance spatial repellent development into practical products. Behavioral avoidance responses were observed for adult laboratory strains of Aedes aegypti, Anopheles minimus and An. dirus, and two field populations of An. harrisoni and Ae. aegypti, respectively. Established TFT sublethal (LC50 and LC75), lethal concentrations (LC99) and discriminating concentrations (DCs) were selected corresponding to each mosquito test species. Spatial repellency and contact excitation ('irritancy') responses on adult mosquitoes to TFT were assessed using an excito-repellency assay system. At LC50, TFT exhibited strong avoidance with An. minimus (60.1% escape) and An. dirus (80% escape) laboratory strains, showing between 12 and 16x greater escape response than Ae. aegypti (5% escape). Repellency responses for field collected Ae. aegypti and An. harrisoni were 54.9 and 47.1% escape, respectively. After adjusting the initial contact escape response (a measure of combined irritancy and repellency) to estimate only escape due to contact, the LC50 and LC99 showed moderate escape irritancy with laboratory Ae. aegypti (41.4% escape) and no contact activity against the field population. Adjustment showed only weak contact activity (16.1% escape) in laboratory An. minimus at LC50. Spatial repellency is the predominant mode of action of TFT among colonized and field mosquitoes used in this study. Established baseline (susceptible) dose-response curves assist in optimizing SR products for mosquito control and pathogen transmission prevention.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ciclopropanos/farmacologia , Fluorbenzenos/farmacologia , Repelentes de Insetos/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Compostos Orgânicos Voláteis/farmacologia , Aedes/efeitos dos fármacos , Aedes/fisiologia , Animais , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Aprendizagem da Esquiva , Relação Dose-Resposta a Droga , Feminino , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Doenças Transmitidas por Vetores/prevenção & controle
6.
Nat Commun ; 11(1): 3764, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724058

RESUMO

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context.


Assuntos
Transtornos Relacionados ao Uso de Álcool/psicologia , Dopamina/metabolismo , Etanol/administração & dosagem , Extinção Psicológica/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Modelos Animais de Doenças , Antagonistas de Dopamina/administração & dosagem , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Comportamento de Procura de Droga/efeitos dos fármacos , Comportamento de Procura de Droga/fisiologia , Extinção Psicológica/efeitos dos fármacos , Feminino , Humanos , Masculino , Ratos , Salicilamidas/administração & dosagem , Técnicas Estereotáxicas , Área Tegmentar Ventral/citologia
7.
J Toxicol Sci ; 45(7): 391-399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612007

RESUMO

This study was aimed at examining propofol- (a known anesthetic) induced emotion-related behavioral disorders in mice, and exploring the possible molecular mechanisms. A total of 60 mice were divided into two groups: control and propofol group. Mice were injected with propofol (150 mg/kg, ip) at 8:00 a.m. (once a day, lasting for 30 days). During the 30 days, loss of righting reflex (LORR) and return of righting reflex (RORR) of mice were recorded every day. At the 1st (T1) and 30th (T2) day of drug discontinuance (T2), 15 mice of each group were selected to perform the open field test; then the mice underwent perfusion fixation, and the midbrain and corpus striatum were separated for immunofluorescence assay with anti-tyrosine hydroxylase (Th) and anti- dopamine transporter (DAT) antibodies. Results showed that after propofol injection, LORR and RORR increased and decreased, respectively. Long-term use of propofol resulted in decreased activities of mice (activity trajectory, line crossing, rearing time, scratching times and defecating frequency). Immunofluorescence assay showed long-term use of propofol induced decrease of Th and DAT. Collectively, our present work suggested long-term abuse of propofol induces neuropsychiatric function impairments, and the possible mechanisms are related to dopamine dyssynthesis via down-regulating tyrosine hydroxylase and dopamine transporter.


Assuntos
Anestésicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Transtornos Mentais/induzido quimicamente , Propofol/toxicidade , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/patologia , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologia , Anestésicos/efeitos adversos , Animais , Neurônios Dopaminérgicos/metabolismo , Emoções/efeitos dos fármacos , Masculino , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Camundongos Endogâmicos C57BL , Propofol/efeitos adversos , Reflexo de Endireitamento/efeitos dos fármacos
8.
Life Sci ; 258: 118139, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32721463

RESUMO

AIMS: Atopic dermatitis is a chronic inflammatory disease characterized by eczematous lesions and has become a serious health problem worldwide. Pseudoephedrine (PSE) is a nasal decongestant to treat the common cold. PSE has been reported that is beneficial to allergic diseases. However, whether PSE has the potential in atopic dermatitis remains to be elucidated. MAIN METHODS: Male BALB/c mice were challenged with 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like lesion and orally administrated with PSE for two weeks. The skin hydration and the scratching behavior were detected. The skin lesions and histopathological changes were evaluated and inflammatory factors levels were detected. Human Keratinocytes (HaCaT cells) were stimulated by TNF-α/IFN-γ after PSE-pretreatment. The transcriptions of inflammatory factors were detected. KEY FINDINGS: PSE decreased skin lesion area and skin thickness in atopic dermatitis mice. PSE improved skin hydration and scratching. Histologically, PSE reduced mast cell and CD4+ cell infiltration. PSE suppressed serum TNF-α and IgE levels, reducing cytokines (IL-1ß, IL-4, IL-6, IL-13, IL-33, TSLP, and IL-23) and neutrophil migration factors (CCL2 and MMP-9) in skin tissues. In addition, PSE inhibited TNF-α/IFN-γ-induced release of inflammatory factors (TNF-α, IL-1ß, and IL-23) in HaCaT cells. Furthermore, PSE suppressed the activation of MAPKs and NF-κB signaling pathways in vivo and in vitro. SIGNIFICANCE: These results demonstrate that PSE could inhibit inflammatory responses in atopic dermatitis models. PSE may serve as a viable alternatives drug for the treatment of atopic dermatitis.


Assuntos
Dermatite Atópica/tratamento farmacológico , Inflamação/tratamento farmacológico , Pseudoefedrina/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Dermatite Atópica/sangue , Dermatite Atópica/enzimologia , Dermatite Atópica/patologia , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/patologia , Interferon gama/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Pseudoefedrina/química , Pseudoefedrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/farmacologia
10.
Life Sci ; 257: 118076, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32659371

RESUMO

AIMS: Huntington's disease is a rare neurodegenerative disorder which is associated with defected glucose metabolism with consequent behavioral disturbance including memory and locomotion. 3-nitropropionic acid (3-NP) can cause, in high single dose, an acute striatal injury/Huntington's disease. Dapagliflozin, which is one of the longest duration of action of SGLTIs family, may be able to diminish that injury and its resultant behavioral disturbances. MATERIAL AND METHODS: Forty rats were divided into four groups (n = 10 in each group): normal control group (CTRL), dapagliflozin (CTRL + DAPA) group, 3-nitropropionic acid (3-NP) group, and dapagliflozin plus 3-nitropropionic acid (DAPA + 3-NP) group. Behavioral tests (beam walking test, hanging wire test, limb withdrawal test, Y-maze spontaneous alteration, elevated plus maze) were performed with evaluating neurological scoring. In striatum, neurotransmitters (glutamate, aspartate, GABA, ACh and AChE activity) were measured. In addition, apoptosis and glycolysis markers (NF-κB, Cyt-c, lactate, HK-II activity, P53, calpain, PEA15 and TIGAR) were determined. Inflammation (IL-1ß, IL-6, IL-8 and TNF-α) and autophagy (beclin-1, LC3 and DRAM) indicators were measured. Additionally, histopathological screening was conducted. KEY FINDINGS: 3-Nitropropionic acid had the ability to perturb the neurotransmission which was reflected in impaired behavioral outcome. All of glycolysis, apoptosis and inflammation markers were elevated after 3-NP acute intoxication but autophagy parameters, except DRAM, were reduced. However, DAPA markedly reversed the abovementioned parameters. SIGNIFICANCE: Dapagliflozin demonstrated anti-glycolytic, anti-apoptotic, anti-inflammatory and autophagic effects on 3-NP-damaged striatal cells and promoted the behavioral outcome.


Assuntos
Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Glicólise/efeitos dos fármacos , Doença de Huntington/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Autofagia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Doença de Huntington/fisiopatologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Ratos Wistar
11.
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
12.
PLoS One ; 15(7): e0236251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692754

RESUMO

This study investigated the effects of kaempferol and zinc gluconate on neurobehavioural and oxidative stress changes in Wistar rats exposed to noise. Thirty (30) rats were randomly divided into five groups: Groups I and II were administered with deionized water (DW); Group III, kaempferol (K); Group IV, zinc gluconate (Zn); Group V, kaempferol + zinc gluconate. Groups II, III, IV, and V were subjected to noise stress (N) induced by exposing rats to 100 dB (4 h/day) for 15 days, from day 33 to day 48 after starting the drug treatments. Neuromuscular coordination, motor coordination, motor strength, sensorimotor reflex, and learning and memory, were evaluated using standard laboratory methods. Levels of nitric oxide (NO), malondialdehyde (MDA) and activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were evaluated in the hippocampus. Exposure of rats to noise, induced significant neurobehavioural deficits and oxidative stress while the combined administration of kaempferol and zinc gluconate significantly (P < 0.05) improved open-field performance, motor coordination, motor strength, sensorimotor reflex, and learning and memory. Co-administration of kaempferol and zinc gluconate ameliorated noise-induced oxidative stress as demonstrated by the significantly increased activities of GPx, catalase, and SOD, and decreased levels of NO and MDA (P < 0.05 and P < 0.01 respectively), compared to the DW + N group. Our results suggest that oxidative stress, evidenced by increased NO and MDA concentration and decreased activities of GPx, catalase and SOD, were involved in the molecular mechanism underlying neurobehavioural impairment in Wistar rats, exposed to noise stress. Single treatment of kaempferol exerted a more potent mitigative effect than zinc gluconate, while their combination produced an improved outcome.


Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Gluconatos/farmacologia , Quempferóis/farmacologia , Ruído/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiopatologia , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Reflexo/efeitos dos fármacos , Zinco/farmacologia
13.
PLoS One ; 15(7): e0235630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628739

RESUMO

In several phytophagous hemipterans, behavior appears to be mediated by both visual and chemical cues. For the Asian citrus psyllid (ACP) Diaphorina citri (Hemiptera: Liviidae), olfactometric assays are generally difficult to interpret owing to the low proportion of individuals responding to odors (~30-40%), which compromises the efficiency and reliability of the results of behavioral tests. In the present study, the ACP behavioral response to emitted odors from sweet orange (Citrus sinensis L. Osbeck) flushes in a 4-arm olfactometer using different colors (four white-, two white- and two yellow- on opposite sides, or four yellow-colored fields), and the role of the airflow in the concentration of volatile organic compounds (VOCs) were assessed at two airflows [0.4 and 0.1 L/min (LPM)]. Exposure to 'Pera' sweet orange or clean air in treatments with four yellow-colored-fields increased the response rate of ACP females to the odor sources compared with exposure to 'Pera' sweet orange or clean air in treatments with four white-colored-fields, independently of the odor source and airflow tested. For the assays using two white- and two yellow-colored fields on opposite sides and 0.4 or 0.1 LPM airflow, the residence time of ACP females to odors ('Pera' sweet orange or clean air) was similar or higher in treatments using yellow- than those using white-colored fields. For both assays (VOCs and olfactometric behavioral parameters), the reduction in airflow from 0.4 to 0.1 LPM greatly changed the airborne concentration and ACP behavior. Quantitative chemical analyses revelead that the concentration of most compounds emitted by 'Pera' sweet orange flushes for the headspace using 0.1 LPM airflow were greater than the concentrations measured using 0.4 LPM airflow. Therefore, this treatment design provides an useful tool to assess the ACP behavioral response to the odors from citrus plants, and it can also help in the discrimination of dose-response screenings for VOCs or conspecific insects.


Assuntos
Ar , Comportamento Animal/efeitos dos fármacos , Citrus/metabolismo , Hemípteros/efeitos dos fármacos , Hemípteros/fisiologia , Olfato , Compostos Orgânicos Voláteis/farmacologia , Animais , Cor , Relação Dose-Resposta a Droga , Compostos Orgânicos Voláteis/metabolismo
14.
Aquat Toxicol ; 226: 105555, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645607

RESUMO

Fish strongly rely on olfaction as a variety of essential behaviors such as foraging and predator avoidance are mediated by the olfactory system. Cadmium (Cd) is known to impair olfaction and accumulate in the olfactory epithelium (OE) and bulb (OB) of fishes. In the present study, the acute toxicity of Cd on olfaction in zebrafish (Danio rerio) was characterized on the molecular and behavioral level. To this end, quantitative real-time PCR was performed in order to analyze the expression of selected genes in both the OE and OB. Moreover, the response of zebrafish to an alarm cue was investigated. Following 24 h of exposure to Cd, the expression of genes associated with olfactory sensory neurons was reduced in the OE. Furthermore, the antioxidant genes peroxiredoxin 1 (prdx1) and heme oxygenase 1 (hmox1), as well as the metallothionein 2 gene (mt2) were upregulated in the OE, whereas hmox1 and the stress-inducible heat shock protein 70 gene (hsp70) were upregulated in the OB upon exposure to Cd. Following stimulation with a conspecific skin extract, zebrafish displayed a considerable disruption of the antipredator behavior with increasing Cd concentration. Taken together, Cd impaired olfaction in zebrafish, thereby disrupting the antipredator response, which is crucial for the survival of individuals. Cellular stress followed by disruption of olfactory sensory neurons may have contributed to the observed behavioral deficits.


Assuntos
Comportamento Animal/efeitos dos fármacos , Cádmio/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Olfato/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Antioxidantes/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Metalotioneína/genética , Metalotioneína/metabolismo , Mucosa Olfatória/efeitos dos fármacos , Olfato/genética , Peixe-Zebra/genética , Peixe-Zebra/fisiologia
15.
J Stroke Cerebrovasc Dis ; 29(8): 104977, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689608

RESUMO

BACKGROUND: Ischemic stroke is a severe neurological disorder that affected millions of people worldwide. Neuro-inflammation and apoptosis play an essential role in the pathogenesis of neuronal death during ischemic stroke. Alpha-pinene is a bicyclic terpenoid with anti-inflammatory and anti-apoptotic activities. Accordingly, the main purpose of this study was to assess the protective effect of α-pinene in ischemic stroke. MATERIALS AND METHODS: To induce ischemic stroke in male Wistar rats, the middle cerebral artery was occluded for 60 min followed by 24 h reperfusion. Alpha-pinene was injected intraperitoneally at the beginning of reperfusion. A day after reperfusion, the neurological deficits, volume of infarct area, and blood-brain barrier (BBB) permeability were evaluated. The mRNA expression of inflammatory cytokines as well as pro- and anti-apoptotic genes was assessed by using reverse transcription-polymerase chain reaction. The protein levels of inflammatory cytokines were also measured by ELISA method. RESULTS: The results showed that α-pinene (50 and 100 mg/kg) significantly improved sensorimotor function and decreased the volume of infarct area in the brain. The high permeability of BBB was also alleviated by α-pinene (50 and 100 mg/kg) in ischemic areas. Besides, α-pinene (100 mg/kg) attenuated neuro-inflammation through decreasing both the gene and protein expression of TNF-α and IL-1ß in the hippocampus, cortex, and striatum. Besides, α-pinene (100 mg/kg) suppressed apoptosis via downregulation of the pro-apoptotic Bax mRNA expression with a concomitant upregulation of anti-apoptotic Bcl-2 gene expression. CONCLUSIONS: Overall, it was concluded that α-pinene exerts neuroprotective effect during ischemic stroke through attenuating neuroinflammation and inhibition of apoptosis.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Monoterpenos Bicíclicos/farmacologia , Encéfalo/efeitos dos fármacos , Citocinas/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Permeabilidade Capilar/efeitos dos fármacos , Citocinas/genética , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
16.
J Thorac Cardiovasc Surg ; 160(2): e55-e66, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689704

RESUMO

OBJECTIVES: This study aims to evaluate the protective effects of progesterone on white matter injury and brain immaturity in neonatal rats with chronic hypoxia. METHODS: Three-day old Sprague-Dawley rats were randomly divided into 3 groups: (1) control (n = 48), rats were exposed to normoxia (fraction of inspired oxygen: 21% ± 0%); (2) chronic hypoxia (n = 48), rats were exposed to hypoxia (fraction of inspired oxygen: 10.5% ± 1.0%); and (3) progesterone (n = 48), rats were exposed to hypoxia and administrated with progesterone (8 mg/kg/d). Hematoxylin-eosin staining, immunohistochemistry, real-time quantitative polymerase chain reaction, and Western blot analyses were compared on postnatal day 14 in different groups. Motor skill and coordination abilities of rats were assessed via rotation experiments. RESULTS: Increased brain weights (P < .05), narrowed ventricular sizes (P < .01), and rotarod experiment scores (P < .01) were better in the progesterone group than in the chronic hypoxia group. The number of mature oligodendrocytes and myelin basic protein expression increased in the progesterone group compared with the chronic hypoxia group (P < .01). The polarization of M1 microglia cells in the corpus callosum of chronic hypoxia-induced hypomyelination rats was significantly increased, whereas there were fewer M2 microglia cells. Conversely, progesterone therapy had an opposite effect and caused an increase in M2 microglia polarization versus a reduction in M1 microglia cells. CONCLUSIONS: Progesterone could prevent white matter injury and improve brain maturation in a neonatal hypoxic rat model; this may be associated with inducing a switch from M1 to M2 in microglia.


Assuntos
Encéfalo/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Leucoencefalopatias/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Progesterona/farmacologia , Substância Branca/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Plasticidade Celular/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Feminino , Hipóxia/metabolismo , Hipóxia/patologia , Hipóxia/fisiopatologia , Leucoencefalopatias/metabolismo , Leucoencefalopatias/patologia , Leucoencefalopatias/fisiopatologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Ratos Sprague-Dawley , Substância Branca/metabolismo , Substância Branca/patologia , Substância Branca/fisiopatologia
17.
Life Sci ; 256: 117892, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32502538

RESUMO

BACKGROUND: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkß pathway in the prefrontal cortex of malathion-exposed rats were tested. METHODS: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures. RESULTS: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkß and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN. CONCLUSION: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkß signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion.


Assuntos
Acetilcolinesterase/metabolismo , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Indóis/farmacologia , Malation/toxicidade , Receptor trkB/metabolismo , Transdução de Sinais , Animais , Antidepressivos/administração & dosagem , Antidepressivos/química , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Indóis/administração & dosagem , Indóis/química , Indóis/uso terapêutico , Masculino , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
18.
J Vis Exp ; (159)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32478732

RESUMO

Alcohol use disorder (AUD) remains a serious problem in our society. To develop effective interventions for addiction, it is important to understand the underlying neurobiological mechanisms, for which diverse experimental approaches and model systems are needed. The main ingredient of alcoholic beverages is ethanol, which causes adaptive changes in the central nervous system and behavior upon chronic intake. Behavioral sensitization (i.e., escalated responses) in particular represents a key adaptive change underlying addiction. Most ethanol-induced behavioral sensitization studies in animal models have been conducted on the locomotor activating effect of ethanol. A prominent effect of ethanol is behavioral disinhibition. Behavioral sensitization to the disinhibition effect of ethanol, however, is underrepresented. To address this issue, we developed the Flypub assay that allows measuring the escalated increase in disinhibited courtship activities upon recurring ethanol exposure in Drosophila melanogaster. Here, we report the step-by-step Flypub assay including assembly of ethanol exposure chambers, setup of the assay station, criteria for fly care and collection, ethanol delivery, quantification of disinhibited courtship activities, data processing and statistical analysis. Also provided are how to troubleshoot critical steps, overcome limitations and expand its utility to assess additional ethanol-induced behaviors. The Flypub assay in combination with powerful genetic tools in Drosophila melanogaster will facilitate the task of discovering the mechanism underlying ethanol-induced behavioral sensitization.


Assuntos
Alcoolismo/etiologia , Comportamento Animal/efeitos dos fármacos , Etanol/efeitos adversos , Animais , Modelos Animais de Doenças
19.
Ecotoxicol Environ Saf ; 201: 110855, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540620

RESUMO

Total dissolved gas (TDG) supersaturation generated by discharged flood water may cause the death of fish downstream of dams and severely threaten their survival during the flood season. No study has performed to investigate the effects of TDG on fish dwelling in shallows in China. Furthermore, varied TDG levels are caused by the varied flow of flood water during the spill season. Fish may alternatingly experience intermittent TDG exposure from equilibrated water and TDG-supersaturated water. However, little research on the effects of intermittent TDG exposure on fish has been conducted. To evaluate the tolerance of fish to continuous acute TDG exposure, juvenile yellow catfish living in the shallows were exposed to TDG-supersaturated water at 125%, 130%, 135% and 140% TDG for 96 h. The results showed that the juvenile yellow catfish exhibited obvious gas bubble disease (GBD) and abnormal behaviours (e.g., exophthalmos and bubbles on fins). The survival probability declined with the arising TDG levels. The median survival time (ST50) of yellow catfish was 8.57, 18.1, 33.86 and 58.84 h at above TDG levels, respectively. To further investigate the effects of intermittent TDG exposure on juvenile yellow catfish, the fish were subjected to varied TDG levels (125%, 130%, 135% and 140%) for a specific duration (3 h and 6 h) and then underwent a period of recovery (3, 6 and 9 h) in equilibrated water. The results showed that an increase in recovery time (or decreasing exposure time) can prolong the survival time of yellow catfish and improve their survival probability at the same exposure time (or same recovery time). Compared with that under continuous acute exposure, the ST50 of juvenile yellow catfish increased significantly with intermittent exposure. Intermittent exposure can enhance the tolerance of juvenile yellow catfish to TDG. The application of the results may contribute to the protection of aquatic organisms and the formulation of the scheme of reservoir operation in the Yangtze River.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Peixes-Gato/fisiologia , Gases/toxicidade , Rios/química , Poluentes da Água/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , China , Gases/análise , Probabilidade , Análise de Sobrevida , Movimentos da Água , Poluentes da Água/análise , Qualidade da Água
20.
Chemosphere ; 258: 127383, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32559491

RESUMO

The application of pesticides typically leads to lethal and sublethal exposure of non-target insects. Whereas our current understanding of these sublethal effects typically focuses on reproductive and physiological parameters, recent works emphasize that sublethal effects on behaviors such as maternal care could be of major importance in non-target species. However, it remained unknown whether these sublethal effects occur in insects. Here, we tested if exposure to sublethal doses of deltamethrin - a pyrethroid insecticide commonly used in crops - alters the expression of maternal egg care in females of the European earwig Forficula auricularia, a predator insect and pest control. Our results first reveal that deltamethrin exposure impaired the expression of three forms of maternal egg care: It decreased the likelihood of mothers to gather their otherwise scattered clutch of eggs, increased the time during which the female abandoned the clutch after a predator attack and reduced egg grooming duration. These sublethal effects did not reflect a lower activity of deltamethrin-exposed females, as these females increased their expression of self-grooming, and deltamethrin exposure did not affect females' exploration and mobility. Finally, we found that the negative effects of deltamethrin on egg care did not modify egg development, hatching rate and juvenile weight, possibly due to the transient effects of deltamethrin on maternal behaviors. Overall, our results reveal that sublethal exposure to a pesticide may diminish maternal egg care in a natural pest control and call for the integration of this measurement in assays on pesticides application.


Assuntos
Comportamento Animal/efeitos dos fármacos , Insetos/efeitos dos fármacos , Inseticidas/toxicidade , Comportamento Materno/efeitos dos fármacos , Nitrilos/toxicidade , Óvulo/crescimento & desenvolvimento , Piretrinas/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Insetos/fisiologia , Reprodução/efeitos dos fármacos
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