: Status epilepticus (SE) is a condition in which seizures are not self-terminating and thereby pose a serious threat to the patient's life. The molecular mechanisms underlying SE are likely heterogeneous and not well understood. Here, we reveal a role for the RNA-binding protein Fragile X-Related Protein 2 (FXR2P) in SE. Fxr2 KO mice display reduced sensitivity specifically to kainic acid-induced SE. Immunoprecipitation of FXR2P coupled to next-generation sequencing of associated mRNAs shows that FXR2P targets are enriched in genes that encode glutamatergic post-synaptic components. Of note, the FXR2P target transcriptome has a significant overlap with epilepsy and SE risk genes. In addition, Fxr2 KO mice fail to show sustained ERK1/2 phosphorylation induced by KA and present reduced burst activity in the hippocampus. Taken together, our findings show that the absence of FXR2P decreases the expression of glutamatergic proteins, and this decrease might prevent self-sustained seizures.

Lo, A.c., Rajan, N., Gastaldo, D., Telley, L., Hilal, M.l., Buzzi, A., et al. (2021). Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures. EMBO REPORTS, 22(4), 1-15 [10.15252/embr.202051404].

Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures

Bagni, Claudia
2021-04-07

Abstract

: Status epilepticus (SE) is a condition in which seizures are not self-terminating and thereby pose a serious threat to the patient's life. The molecular mechanisms underlying SE are likely heterogeneous and not well understood. Here, we reveal a role for the RNA-binding protein Fragile X-Related Protein 2 (FXR2P) in SE. Fxr2 KO mice display reduced sensitivity specifically to kainic acid-induced SE. Immunoprecipitation of FXR2P coupled to next-generation sequencing of associated mRNAs shows that FXR2P targets are enriched in genes that encode glutamatergic post-synaptic components. Of note, the FXR2P target transcriptome has a significant overlap with epilepsy and SE risk genes. In addition, Fxr2 KO mice fail to show sustained ERK1/2 phosphorylation induced by KA and present reduced burst activity in the hippocampus. Taken together, our findings show that the absence of FXR2P decreases the expression of glutamatergic proteins, and this decrease might prevent self-sustained seizures.
7-apr-2021
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
ERK signaling
glutamatergic synapses
kainic acid
status epilepticus
FXR2P
Lo, A.c., Rajan, N., Gastaldo, D., Telley, L., Hilal, M.l., Buzzi, A., et al. (2021). Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures. EMBO REPORTS, 22(4), 1-15 [10.15252/embr.202051404].
Lo, Ac; Rajan, N; Gastaldo, D; Telley, L; Hilal, Ml; Buzzi, A; Simonato, M; Achsel, T; Bagni, C
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/315925
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