Abstract
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.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.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.Taken together, the present study suggests that the blockade of the p75 receptor may affect the irritability and anxiety-related behavior in a rat model of status epilepticus.
Highlights
EPilepsy is one of the most common neurological disorders with a prevalence of 1% in the general population
Since p75NTR is up-regulated following induction of SE[42] and may be involved in several psychiatric diseases[17,25]; we here asked whether the blockage of p75NTR would ameliorate behavioral changes associated with pilocarpine treatment in a rat model of SE
In line with previous investigations in epileptic rats[42,44,45,46], we demonstrated here the up-regulation of mRNA expressions of p75NTR and pro-nerve growth factor (NGF) in a rat pilocarpine-induced SE model, which in turn is associated with the elevated level of aggressive behavior
Summary
EPilepsy is one of the most common neurological disorders with a prevalence of 1% in the general population. Studies have shown that the prevalence of psychiatric disorders in patients with epilepsy is more frequent than that in general population[1,2]. 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. 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. Results: Molecular findings indicated a high level of mRNA expression for both p75 receptors and pro-NGF in the epileptic model group. 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.
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