RESUMO
Fipronil (Fpl), an insecticide belonging to the class of phenylpyrazoles, is associated with the widespread mortality of pollinator insects worldwide. Based on studies carried out on residual concentrations of Fpl commonly found in the environment, in this study, we evaluated the sublethal effects of Fpl on behavior and other neurophysiological parameters using the cockroach Nauphoeta cinerea as a biological model. Sublethal doses of Fpl (0.1-0.001â µg g-1) increased the time spent grooming and caused dose-dependent inhibition of exploratory activity, partial neuromuscular blockade in vivo and irreversible negative cardiac chronotropism. Fpl also disrupted learning and olfactory memory formation at all doses tested. These results provide the first evidence that short-term exposure to sublethal concentrations of Fpl can significantly disrupt insect behavior and physiology, including olfactory memory. These findings have implications for current pesticide risk assessment and could be potentially useful in establishing a correlation with pesticide effects in other insects, such as honey bees.
Assuntos
Baratas , Inseticidas , Praguicidas , Abelhas , Animais , Inseticidas/toxicidade , Pirazóis/farmacologia , Praguicidas/farmacologiaRESUMO
Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca2+ concentrations ([Ca2+]i) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures. Alterations in [Ca2+]i were detected by changes in the Fluo-4 AM reagent emission. PYY (3-36) significantly increased [Ca2+] from the concentration of 10-11M as compared to the controls (infusion of HEPES-buffered solution (HBS) solution alone). The PYY (3-36)-increase in [Ca2+]i remained unchanged even in Ca2+-free extracellular solutions. Sarcoplasmic/endoplasmic reticulum Ca2+-ATPase pump (SERCA pump) inhibition partially prevent the PYY (3-36)-increase of [Ca2+]i and inositol 1,4,5-triphosphate receptor (IP3R) inhibition also decreased the PYY (3-36)-increase of [Ca2+]i. Taken together, our data strongly suggest that PYY (3-36) mobilizes calcium from the neuronal endoplasmic reticulum (ER) stores towards the cytoplasm. Next, we showed that PYY (3-36) inhibited high K+-induced increases of [Ca2+]i, suggesting that PYY (3-36) could also act by activating G-protein coupled inwardly rectifying potassium K+ channels. Finally, the co-infusion of the Y2 receptor (Y2R) antagonist BIIE0246 with PYY (3-36) abolished the [Ca2+]i increase induced by the peptide, suggesting that PYY (3-36)-induced [Ca2+]i increase in hippocampal neurons occurs via Y2Rs.
Assuntos
Cálcio/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo YY/metabolismo , Fosfatidilinositóis/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Benzazepinas/farmacologia , Citoplasma/metabolismo , Feminino , Masculino , Neuropeptídeo Y/metabolismo , Polipeptídeo Pancreático/metabolismo , Ratos Wistar , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Neuropeptídeo Y/metabolismoRESUMO
It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca2+]i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats.
Assuntos
Potenciação de Longa Duração/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilprednisolona/farmacologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Cálcio/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Memória/classificação , Memória/fisiologia , Metilprednisolona/metabolismo , Ratos , Ratos Wistar , Sinapses/fisiologiaRESUMO
Organophosphate (OP) insecticides have been used indiscriminately, based on their high dissipation rates and low residual levels in the environment. Despite the toxicity of OPs to beneficial insects is principally devoted to the acetylcholinesterase (AChE) inhibition, the physiological mechanisms underlying this activity remain poorly understood. Here we showed the pharmacological pathways that might be involved in severe alterations in the insect locomotion and grooming behaviors following sublethal administration of the OP Trichlorfon (Tn) (0.25, 0.5 and 1 µM) in Phoetalia pallida. Tn inhibited the acetylcholinesterase activity (46±6, 38±3 and 24±6 nmol NADPH/min/mg protein, n=3, p<0.05), respectively. Tn (1 µM) also increased the walking maintenance of animals (46±5 s; n=27; p<0.05). Tn caused a high increase in the time spent for this behavior (344±18 s/30 min, 388±18 s/30 min and 228±12 s/30 min, n=29-30, p<0.05, respectively). The previous treatment of the animals with different cholinergic modulators showed that pirenzepine>atropine>oxotremorine>d-tubocurarine>tropicamide>methoctramine induced a decrease on Tn (0.5 µM)-induced grooming increase, respectively in order of potency. Metoclopramide (0.4 µM), a DA-D2 selective inhibitor decreased the Tn-induced grooming activity (158±12 s/30 min; n=29; p<0.05). Nevertheless, the effect of the selective DA-D1 receptor blocker SCH 23390 (1.85 µM) on the Tn (0.5 µM)-induced grooming increase was significative and more intense than that of metoclopramide (54±6 s/30 min; n=30; p<0.05). Taken together the results suggest that a cross-talking between cholinergic M1/M3 and dopaminergic D1 receptors at the insect nervous system may play a role in the OP-mediated behavioral alterations.
Assuntos
Baratas/efeitos dos fármacos , Inseticidas/toxicidade , Transmissão Sináptica/efeitos dos fármacos , Triclorfon/toxicidade , Acetilcolinesterase/metabolismo , Animais , Encéfalo/enzimologia , Baratas/metabolismo , Asseio Animal/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacosRESUMO
Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short-chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. In this work, we investigated the in vitro and in vivo EMA effects on Na(+), K(+)-ATPase (NAK) activity and mRNA levels in cerebral cortex from 30-day-old rats. For in vitro studies, cerebral cortex homogenates were incubated in the presence of EMA at 0.5, 1, or 2.5 mM concentrations for 1 h. For in vivo experiments, animals received three subcutaneous EMA injections (6 µmol g(-1); 90-min interval) and were killed 60 min after the last injection. After that, NAK activity and its mRNA expression were measured. We observed that EMA did not affect this enzyme activity in vitro. In contrast, EMA administration significantly increased NAK activity and decreased mRNA NAK expression as assessed by semiquantitative reverse transcriptase polymerase chain reaction when compared with control group. Considering the high score of residues prone to phosphorylation on NAK, this profile can be associated with a possible regulation by specific phosphorylation sites of the enzyme. Altogether, the present results suggest that NAK alterations may be involved in the pathophysiology of brain damage found in patients in which EMA accumulates.