ArticleCell & bioscience2020
Lrp4 in hippocampal astrocytes serves as a negative feedback factor in seizures.
Article in Cell & bioscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 7 citations in OpenAlex.
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- Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling.Cell & bioscience · 2024Article
- The intricate dance of non-coding RNAs in myasthenia gravis pathogenesis and treatment.Frontiers in immunology · 2024Review
- Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEpilepsy is characterized by the typical symptom of seizure, and anti-seizure medications are the main therapeutic method in clinical, but the effects of these therapy have not been satisfactory. To find a better treatment, it makes sense to further explore the regulatory mechanisms of seizures at genetic level. Lrp4 regionally expresses in mice hippocampus where is key to limbic epileptogenesis. It is well known that neurons release a high level of glutamate during seizures, and it has been reported that Lrp4 in astrocytes down-regulates glutamate released from neurons. However, it is still unclear whether there is a relationship between Lrp4 expression level and seizures, and whether Lrp4 plays a role in seizures.
resultsWe found that seizures induced by pilocarpine decreased Lrp4 expression level and increased miR-351-5p expression level in mice hippocampus. Glutamate reduced Lrp4 expression and enhanced miR-351-5p expression in cultured hippocampal astrocytes, and these effects can be partially attenuated by AP5. Furthermore, miR-351-5p inhibitor lessened the reduction of Lrp4 expression in glutamate treated hippocampal astrocytes. Local reduction of Lrp4 in hippocampus by sh Lrp4 lentivirus injection in hippocampus increased the threshold of seizures in pilocarpine or pentylenetetrazol (PTZ) injected mice.
conclusionsThese results indicated that high released glutamate induced by seizures down-regulated astrocytic Lrp4 through increasing miR-351-5p in hippocampal astrocytes via activating astrocytic NMDA receptor, and locally reduction of Lrp4 in hippocampus increased the threshold of seizures. Lrp4 in hippocampal astrocytes appears to serve as a negative feedback factor in seizures. This provides a new potential therapeutic target for seizures regulation.
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