Abstract

Excessive excitation or loss of inhibitory neurotransmission has been closely related to epileptic activity. Somatostatin (SST) and Neuropeptide Y (NPY) are members of endogenous neuropeptides which are recognized as important modulator of classical neurotransmitter, distributed abundantly in mammalian central nervous system. Abnormal expression of these two neuropeptides evidenced in some epileptic models highlights the relevance of SST or NPY in the pathogenesis of epilepsy. The tremor rat (TRM) is a genetic epileptic animal model which can manifest tonic convulsions without any external stimuli. The present study aimed to investigate the distribution and expression of SST and NPY in TRM brains, including hippocampus, temporal lobe cortex and cerebellum. Our RT‑PCR data showed that up-regulated mRNA expression of SST and NPY was discovered in TRM hippocampus and temporal lobe cortex compared with control (Wistar) rats. The peptide levels of these neuropeptides in brain areas mentioned above were both apparently higher than that in normal Wistar rats as well. However, in cerebellums, neither SST nor NPY was significantly changed compared with control group. The immunohistochemical data showed that SST and NPY were widely present throughout CA1, CA3 and the hilus of hippocampus, the entorhinal cortex of temporal lobe cortex, as well as cerebellar Purkinje layer. In conclusion, our results discovered the aberrant changes of SST and NPY in several TRM brain regions, suggesting that the peptidergic system might be involved in TRM epileptiform activity.

Highlights

  • Epilepsy is one of the most common chronic neurological disorders which is characterized by recurrent and unprovoked seizures, affecting over 70 million people worldwide (Weaver and Pohlmann-Eden 2013, Erfanparast and Tamaddonfard 2015)

  • Somatostatin (SST) and neuropeptide Y (NPY) are both belonged to endogenous neuropeptides family, abundantly express in neurons of brain areas and are likely to be preferentially released by neurons subjected to high-frequency stimulation

  • In the present study, we focused on the expression and distribution of SST and NPY in tremor rat (TRM) brain areas, including hippocampus, temporal lobe cortex and cerebellum in order to explore the potential role of neuropeptides in TRM epileptogenesis

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Summary

Introduction

Epilepsy is one of the most common chronic neurological disorders which is characterized by recurrent and unprovoked seizures, affecting over 70 million people worldwide (Weaver and Pohlmann-Eden 2013, Erfanparast and Tamaddonfard 2015). As the modulators of classical neurotransmitters, such as γ-aminobutyric acid (GABA) and glutamate (GLU), neuropeptides are closely linked to epileptic diseases, including pathogenesis and treatment. Somatostatin (SST) and neuropeptide Y (NPY) are both belonged to endogenous neuropeptides family, abundantly express in neurons of brain areas and are likely to be preferentially released by neurons subjected to high-frequency stimulation. The role of SST in seizure is first confirmed by temporal lobe epileptic rats in which SST-containing neurons in the hilus of dentate gyrus are selectively lost (Sloviter 1987). The expression of SST could be markedly affected in response to seizure occurrence. In convulsive rats induced by repeated amygdaloid kindling, remarkably elevated expression of SST could be observed in epileptic models evoked by lidocaine and electroconvulsive stimulation (Nagaki et al 2000, Mikkelsen and Woldbye 2006). Adeno-associated viral vector-mediated overexpression of SST and SST agonists

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