18 research outputs found

    N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

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    Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extrasynaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet. Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish. Results: NAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects. Discussion: NAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD

    Efeito do tratamento com l?tio sobre a habilidade motora e o sistema Wnt-catenina-caderina durante o desenvolvimento inicial de Zebrafish

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    Made available in DSpace on 2015-04-14T14:51:10Z (GMT). No. of bitstreams: 1 432086.pdf: 1674235 bytes, checksum: 2ed5ea531f6750c937a1c83b125d4be9 (MD5) Previous issue date: 2011-03-17L?tio tem sido o principal tratamento para desordens bipolares desde 1950, oferecendo um efeito profil?tico e agudo contra os epis?dios man?acos e depressivos, apesar dos desafios encontrados na sua administra??o durante a gravidez e o per?odo perinatal. Os mecanismo por tr?s dos efeitos do l?tio ainda n?o foram descritos completamente mas existem evidencias de um efeito sobre a via Wnt-?-catenina devido a sua capacidade de inibi??o sobre a GSK-3?. Neste estudo n?s avaliamos os efeitos da exposi??o ao l?tio durante o desenvolvimento inicial de Zebrafish incluindo caracteriza??es comportamentais e moleculares do sistema Wnt-?-catenina-Caderina. Embri?es foram tratados individualmente por 72hpf com LiCl 0.05, 0.5 e 5 mM. N?o foram observadas malforma??es significativas nem efeitos embriot?xicos. Em 10 dpf animais tratados com 0.5 e 5 mM de l?tio demonstraram habilidades locomotoras similares a s?ndrome induzida por l?tio em humanos Floppy baby syndrom. An?lises atrav?s da t?cnica de Western blot demonstraram uma express?o aumentada nos n?veis de ?-catenina e diminu?da para N-caderina. Animais com 10dpf reestabeleceram seus n?veis de express?o proteica de acordo com o controle. An?lises atrav?s da t?cnica de qPCR n?o demonstraram nenhum efeito sobre os n?veis de ?-catenina ou N-caderina, sugerindo a ocorr?ncia de mudan?as p?s-transcricionais. Enquanto os n?veis de c-myc n?o foram alterados, houve uma diminui??o nos n?veis de Cyclin D1 em larvas de 3dpf, enquanto os n?veis de CamkIV ocilara

    Antiepileptic drugs prevent changes in adenosine deamination during acute seizure episodes in adult zebrafish

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    AbstractAdenosine is an endogenous modulator of brain functions, which presents anticonvulsant properties. In addition, its levels can be increased during neural injury. The modulation of extracellular adenosine levels by ectonucleotidase and adenosine deaminase (ADA) activities may represent a key mechanism in the control of epileptogenesis. In the present study, we investigated the effects of acute seizure episodes and antiepileptic drug (AED) treatments on ectonucleotidases and ADA activities in adult zebrafish brain. Our data have demonstrated that pentylenetetrazole (PTZ)-induced seizures did not alter ATP, ADP, and AMP hydrolysis in brain membrane fractions. However, there was a significant increase on ecto-ADA and soluble ADA activities in PTZ-treated animals immediately after a clonus-like convulsion and loss of posture, which are typical behavioral changes observed in Stage 3. Furthermore, our results have demonstrated that AED pretreatments prevented the stimulatory effect promoted by PTZ exposure on ADA activities. The PTZ and AED treatments did not promote alterations on ADA gene expression. Interestingly, when exposed to PTZ, animals pretreated with AEDs showed longer latency to reach the clonus-like seizure status, which is an effect that matches the suppression of the increase of ADA activity promoted by the AEDs. These data suggest that the adenosine deamination could be involved in the control of seizure development in zebrafish and may be modulated by AED treatments
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