SAD-B modulates epileptic seizure by regulating AMPA receptors in patients with temporal lobe epilepsy and in the PTZ-induced epileptic model
Braz. j. med. biol. res
;
53(4): e9175, 2020. tab, graf
Article
Dans Anglais
| LILACS
| ID: biblio-1089352
ABSTRACT
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are the predominant mediators of glutamate-induced excitatory neurotransmission. It is widely accepted that AMPA receptors are critical for the generation and spread of epileptic seizure activity. Dysfunction of AMPA receptors as a causal factor in patients with intractable epilepsy results in neurotransmission failure. Brain-specific serine/threonine-protein kinase 1 (SAD-B), a serine-threonine kinase specifically expressed in the brain, has been shown to regulate AMPA receptor-mediated neurotransmission through a presynaptic mechanism. In cultured rat hippocampal neurons, the overexpression of SAD-B significantly increases the frequency of miniature excitatory postsynaptic currents (mEPSCs). Here, we showed that SAD-B downregulation exerted antiepileptic activity by regulating AMPA receptors in patients with temporal lobe epilepsy (TLE) and in the pentylenetetrazol (PTZ)-induced epileptic model. We first used immunoblotting and immunohistochemistry analysis to demonstrate that SAD-B expression was increased in the epileptic rat brain. Subsequently, to explore the function of SAD-B in epilepsy, we used siRNA to knock down SAD-B protein and observed behavior after PTZ-induced seizures. We found that SAD-B downregulation attenuated seizure severity and susceptibility in the PTZ-induced epileptic model. Furthermore, we showed that the antiepileptic effect of SAD-B downregulation on PTZ-induced seizure was abolished by CNQX (an AMPA receptor inhibitor), suggesting that SAD-B modulated epileptic seizure by regulating AMPA receptors in the brain. Taken together, these findings suggest that SAD-B may be a potential and novel therapeutic target to limit epileptic seizures.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Médicaments issus de plantes chinoises
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Protein-Serine-Threonine Kinases
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Récepteur de l'AMPA
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Agonistes des acides aminés excitateurs
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Épilepsie temporale
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2020
Type:
Article
Pays d'affiliation:
Chine
Institution/Pays d'affiliation:
Capital Medical University/CN
/
First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology/CN
/
Second Affiliated Hospital of Chongqing Medical University/CN
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