Abstract
To explore the effects of neuronal Per-Arnt-Sim domain protein 4 (Npas4) on seizures in pilocarpine-induced epileptic rats, Npas4 expression was detected by double-label immunofluorescence, immunohistochemistry, and Western blotting in the brains of pilocarpine-induced epileptic model rats at 6 h, 24 h, 72 h, 7 d, 14 d, 30 d, and 60 d after status epilepticus. Npas4 was localized primarily in the nucleus and in the cytoplasm of neurons. The Npas4 protein levels increased in the acute phase of seizures (between 6 h and 72 h) and decreased in the chronic phases (between 7 d and 60 d) in the rat model. Npas4 expression was knocked down by specific siRNA interference. Then, the animals were treated with pilocarpine, and the effects on seizures were evaluated on the 7th day. The onset latencies of pilocarpine-induced seizures were decreased, while the seizure frequency, duration and attack rate increased in these rats. Our study indicates that Npas4 inhibits seizure attacks in pilocarpine-induced epileptic rats.
Highlights
Epilepsy often occurs in patients suffering from recurrent seizures, which are usually associated with an imbalance of excitatory and inhibitory neurons in the central nervous system (CNS), as demonstrated by Brenner [4]
Neuronal Per-Arnt-Sim domain protein 4 (Npas4) expression was dynamically detected in a pilocarpine-induced epileptic rat model
The effects of Npas4 on seizures were explored after the down-regulation of the Npas4 expression using siRNA interference
Summary
Epilepsy often occurs in patients suffering from recurrent seizures, which are usually associated with an imbalance of excitatory and inhibitory neurons in the central nervous system (CNS), as demonstrated by Brenner [4]. Epilepsy is known to be resulted from an imbalance between glutamate-mediated excitatory. Npas is expressed in the central nervous system (CNS), which is predominantly restricted to the cortical and hippocampus areas of the rodent brain [21, 25]. Npas has been demonstrated to critically regulate inhibitory synapse formation [15] and to directly control brain-derived neurotrophic factor (BDNF) activity-dependent transcription [24]. Npas plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons [15]. Npas is required for the activity-induced changes in synaptic inputs to these neurons but not for changes to output synapses in their axons [30]
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