Correction: High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy

Pai, Balagopal; Tomé-García, Jessica; Cheng, Wan Sze; Nudelman, German; Beaumont, Kristin G.; Ghatan, Saadi; Panov, Fedor; Caballero, Elodia; Sarpong, Kwadwo; Marcuse, Lara; Yoo, Ji Yeoun; Jiang, Yan; Schaefer, Anne; Akbarian, Schahram; Sebra, Robert; Pinto, Dalila; Zaslavsky, Elena; Tsankova, Nadejda M.

doi:10.1186/s40478-022-01479-5

Cited by 2 publications

(1 citation statement)

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“…Among 36 samples in the GSE134697 dataset [ 39 ], 17 hippocampal and 17 neocortex samples were obtained from patients with drug-resistant temporal lobe epilepsy, whereas 2 neocortex samples were obtained from healthy subjects. Single brain cells from temporal tissues of 5 patients with temporal lobe epilepsy (TLE) were analyzed in GSE140393 [ 40 , 41 ]. Single nuclei of the CA1 area from 2 control and 2 epileptic mice were downloaded from the GSE143560 dataset [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Li,

Quan,

et al. 2024

J Neuroinflammation

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Ferroptosis is an iron-dependent cell death mechanism involving the accumulation of lipid peroxides. As a critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be downregulated in epilepsy. However, the mechanism of ferroptosis in epilepsy remains unclear. In this study, bioinformatics analysis, analysis of epilepsy patient blood samples and cell and mouse experiments revealed strong associations among epilepsy, ferroptosis, microRNA-211-5p and purinergic receptor P2X 7 (P2RX7). P2RX7 is a nonselective ligand-gated homotrimeric cation channel, and its activation mainly increases neuronal activity during epileptic seizures. In our study, the upregulation of P2RX7 in epilepsy was attributed to the downregulation of microRNA (miR)-211-5p. Furthermore, P2RX7 has been found to regulate GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of the MAPK/ERK signaling pathway in murine models. The dynamic decrease in miR-211-5p expression induces hypersynchronization and both nonconvulsive and convulsive seizures, and forebrain miR-211-5p suppression exacerbates long-lasting pentylenetetrazole-induced seizures. Additionally, in this study, induction of miR-211-5p expression or genetic-silencing of P2RX7 significantly reduced the seizure score and duration in murine models through the abovementioned pathways. These results suggest that the miR-211-5p/P2RX7 axis is a novel target for suppressing both ferroptosis and epilepsy.

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Section: Methodsmentioning

confidence: 99%

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Li,

Quan,

et al. 2024

J Neuroinflammation

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Epileptogenesis Inhibits the Circadian Clock and Reshapes the Diurnal Transcriptomic Rhythmicity in the Mouse Hippocampus

Benvenutti,

Bruno,

Gallas-Lopes

et al. 2024

Preprint

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Epileptogenesis is the process that leads the brain into epileptic activity. Clinical evidence shows that ∼90% of people with epilepsy present rhythmicity in the timing of their seizures presentation. However, whether the circadian clock is a key player during epileptogenesis remains unknown. Here, we triggered epileptogenesis in mice by the intra-amygdala injection of kainic acid and profiled by RNA sequencing their hippocampal diurnal mRNA rhythmicity. We show that epileptogenesis largely reshapes the hippocampal transcriptomic rhythmicity and that the molecular clock machinery is inhibited due to the disruption of the core clock geneBmal1. We identified relevant dysregulated pathways and their dynamics in epileptogenesis, predicting a key role for microglial-driven neuroinflammation. We predicted the genes thatBmal1is directly controlling over time. Finally, we sought for translational relevance evidence by performing RNA sequencing in hippocampal samples resected from patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and cross-analyzing datasets.

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Correction: High-resolution transcriptomics informs glial pathology in human temporal lobe epilepsy

Cited by 2 publications

References 1 publication

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress

Epileptogenesis Inhibits the Circadian Clock and Reshapes the Diurnal Transcriptomic Rhythmicity in the Mouse Hippocampus

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