Background: Many recent epidemiological studies have shown that epileptic patients are more likely suffer from depression, anxiety, and irritability. However, the cellular mechanisms of epilepsy-induced psychotic behaviors are not fully elucidated. Neurotrophin receptors have been suggested to be involved in epilepsy and also in psychiatric disorders. Up-regulation of p75NTR expression and activation of p75NTR signalling cascades after the seizure have been shown, but the role of the p75 receptor in epilepsy-induced psychotic behaviors has not been documented so far. Therefore, the present work aimed to investigate the effect of p75 receptor blockade on seizure activity, irritability, and anxiety-like behaviors in a rat model of status epilepticus. Methods: Rats were injected with pilocarpine (350 mg/ kg, i.p.) to induce status epilepticus. Then various behavioral tests were performed after the blockade of p75NTR alone or in combination with p75 antagonist and phenobarbital. Molecular analysis by PCR was performed to investigate the expression of p75 and pro-NGF. Results: Molecular findings indicated a high level of mRNA expression for both p75 receptors and pro-NGF in the epileptic model group. Results also showed that the administration of p75 antagonist alone or in combination with phenobarbital was able to significantly influence the behavioral responses. Furthermore, 20-hours video monitoring showed a decrease in the frequency and duration of seizures in the rat group receiving p75 antagonist. Conclusion: Taken together, the present study suggests that the blockade of the p75 receptor may affect the irritability and anxietyrelated behavior in a rat model of status epilepticus.
It is a long time that natural toxin research is conducted to unlock the medical potential of toxins. Although venoms-toxins cause pathophysiological conditions, they may be effective to treat several diseases. Since toxins including scorpion toxins target voltagegated ion channels, they may have profound effects on excitable cells. Therefore, elucidating the cellular and electrophysiological impacts of toxins, particularly scorpion toxins would be helpful in future drug development opportunities. Methods: Intracellular recording was made from F1 cells of Helix aspersa in the presence of calcium Ringer solution in which Na + and K + channels were blocked. Then, the modulation of channel function in the presence of extracellular application of F4 and F6 toxins and kaliotoxin (KTX; 50 nM and 1 μM) was examined by assessing the electrophysiological characteristics of calcium spikes. Results: The two active toxin fractions, similar to KTX, a known Ca 2+-activated K + channel blocker, reduced the amplitude of AHP, enhanced the firing frequency of calcium spikes and broadened the duration of Ca 2+ spikes. Therefore, it might be inferred that these two new fractions induce neuronal hyperexcitability possibly, in part, by blocking calcium-activated potassium channel current. However, this supposition requires further investigation using voltage clamping technique. Conclusion: These toxin fractions may act as blocker of calcium-activated potassium channels.
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