Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome

Oct 14, 2022eNeuro

MicroRNA-134 as a potential target to reduce seizures and sudden death in a mouse model of Dravet syndrome

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Ant-134 treatment had no effect on seizure incidence or mortality in mice.

Dravet syndrome is characterized by severe seizures that are often resistant to treatment.
is involved in regulating gene expression related to brain function.
Inhibiting miR-134 with Ant-134 has previously shown promise in reducing seizures in other models.
The study assessed the effectiveness of Ant-134 in preventing hyperthermia-induced seizures and sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome mice.
No significant changes were observed in seizure incidence or mortality rates in the Ant-134 treated group compared to untreated mice.
The findings indicate that targeting miR-134 may not provide therapeutic benefits for Dravet syndrome.

AI simplified

(DS) is a catastrophic form of pediatric epilepsy mainly caused by noninherited mutations in thegene. DS patients suffer severe and life-threatening focal and generalized seizures which are often refractory to available anti-seizure medication. (ASOs) based approaches may offer treatment opportunities in DS. MicroRNAs are short noncoding RNAs that play a key role in brain structure and function by post-transcriptionally regulating gene expression, including ion channels. Inhibiting miRNA-134 (miR-134) using an antimiR ASO (Ant-134) has been shown to reduce evoked seizures in juvenile and adult mice and reduce epilepsy development in models of focal epilepsy. The present study investigated the levels of miR-134 and whether Ant-134 could protect against hyperthermia-induced seizures, spontaneous seizures and mortality (SUDEP) in F1.+/-mice. At P17, animals were intracerebroventricular injected with 0.1-1 nmol of Ant-134 and subject to a hyperthermia challenge at postnatal day (P)18. A second cohort of P21 F1.+/-mice received Ant-134 and were followed by video and EEG monitoring until P28 to track the incidence of spontaneous seizures and SUDEP. Hippocampal and cortical levels of miR-134 were similar between wild-type (WT) and F1.+/-mice. Moreover, Ant-134 had no effect on hyperthermia-induced seizures, spontaneous seizures and SUDEP incidence were unchanged in Ant-134-treated DS mice. These findings suggest that targeting miR-134 does not have therapeutic applications in DS. SCN1A Scn1a() tm1kea Scn1a() tm1kea Scn1a() tm1kea

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text ↗

Investigation of MicroRNA-134 as a Target against Seizures and SUDEP in a Mouse Model of Dravet Syndrome

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief