Neuroscience
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Whether dopamine (DA) release is compensated during the presymptomatic phase of Parkinson's disease (PD) is controversial. Here we use in vivo voltammetry in the parkinsonian rat and an electrical stimulation protocol established to fatigue nigrostriatal dopaminergic (DAergic) neurons to investigate the plasticity of DA-release mechanisms. Amplitudes of evoked voltammetric signals recorded in intact rat striata decreased with repetitive, high-frequency stimulation (60 Hz, every 5 min/60 min). ⋯ We further demonstrate through kinetic analysis that lesions and compromised uptake target a "long-term" (time constant of minutes) presynaptic depression, which underlies the maintenance of release. Taken together, our findings identify a denervation-induced maintenance of DA release that was independent of activated synthesis and driven by altered uptake. This novel neuroadaptation may contribute to early preclinical normalization of function and help resolve discrepant findings regarding compensatory changes in DA release during progression of the parkinsonian state.
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In this study, we investigated the effects of 2,2'-dithienyl diselenide (DTDS), an organoselenium compound, against seizures induced by kainic acid (KA) in rats. Rats were pretreated with DTDS (50 or 100 mg/kg) by oral route 1 h before KA injection (10 mg/kg, intraperitoneal). Our results showed that DTDS (100 mg/kg) was effective in increasing latency for the onset of the first clonic seizure episode induced by KA, as well as in decreasing the appearance of seizures and the Racine's score. ⋯ Besides, elevated reactive species (RS) and carbonyl protein levels and Na(+), K(+)-ATPase activity in hippocampus of rats treated with KA were ameliorated by DTDS (50 and 100 mg/kg). Lastly, as evidenced by Cresyl-Violet stain, DTDS (100 mg/kg) elicited a protective effect against KA-induced neurodegeneration in rat hippocampus 7 days after KA injection. In conclusion, the present study showed that DTDS attenuated KA-induced status epilepticus in rats and the subsequent hippocampal damage.