RESUMO
Herbicides have been recognized as the main environmental factor associated with human neurodegenerative disorders such as Parkinson's disease(PD). Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanism remains unclear. We investigated the neurotoxic effects of glyphosate in differentiated PC12 cells and discovered that it inhibited viability of differentiated PC12 cells in dose-and time-dependent manners. Furthermore, the results showed that glyphosate induced cell death via autophagy pathways in addition to activating apoptotic pathways. Interestingly, deactivation of Beclin-1 gene attenuated both apoptosis and autophagy in glyphosate treated differentiated PC12 cells, suggesting that Beclin-1 gene is involved in the crosstalk between the two mechanisms.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Proteínas Reguladoras de Apoptose/genética , Proteína Beclina-1 , Western Blotting , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inativação Gênica , Glicina/toxicidade , Células PC12 , Ratos , Fatores de Tempo , GlifosatoAssuntos
Glicina/análogos & derivados , Herbicidas/efeitos adversos , Exposição Ocupacional/efeitos adversos , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Adulto , Indústria Química , Feminino , Glicina/efeitos adversos , Humanos , Transtornos Parkinsonianos/fisiopatologia , GlifosatoRESUMO
Deep brain stimulation (DBS) is now emerging as a new option for treating intractable epilepsy. Cumulative studies suggest that the mediodorsal thalamic nucleus (MD) is involved in limbic seizure activity. This study aims to investigate whether DBS of the MD can protect against seizures induced by amygdaloid kindling. We studied the effect of low-frequency stimulation (LFS, 1 Hz) or high-frequency stimulation (HFS, 100 Hz) in the MD on amygdaloid kindling seizures. During the kindling acquisition, DBS in the MD was daily administered immediately after the kindling stimulus or before the kindling stimulus (preemptive DBS). The effects of both post-treatment of DBS and preemptive DBS in the MD on the expression of amygdaloid kindling seizures were evaluated. We found the DBS or preemptive DBS in the MD, either LFS or HFS, did not significantly change the rate of amygdaloid kindling. Similarly, DBS or preemptive DBS in the MD did not significantly change any parameters representing the expression of amygdaloid kindling. Our study suggests that DBS in the MD may have no significant effect on limbic seizures.