TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy

Mundrucz, Laura; Kecskés, Angela; Henn-Mike, Nóra; Kóbor, Péter; Buzás, Péter; Vennekens, Rudi; Kecskés, Miklós

doi:10.1186/s12915-023-01604-3

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…Biperiden treatment in this model also displayed reduced frequency and severity of spontaneous epileptic seizures, and decreased hippocampal hilus neuronal death [12]. Hilar cell loss is associated with temporal lobe epilepsy, both as a consequence as well as a potential contributor for this type of epilepsy [31,32]. Temporal lobe lesions greatly increase the odds of developing PTE [33], and temporal lobe epilepsy is the most common type of PTE, followed by frontal lobe epilepsy.…”

Section: Discussionmentioning

confidence: 70%

miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury

Villena-Rueda,

Kajitani,

Ota

et al. 2024

Mol Neurobiol

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Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown e cacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE, and act as TBI-and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with 3 subjects developing PTE, and 19 received placebo, with 2 developing PTE. Serum EVs were characterized by size distribution and protein pro ling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no signi cant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These ndings suggest serum miR-9-5p as a possible marker for biperiden treatment, which may play a role in TBI resolution.

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Section: Discussionmentioning

confidence: 70%

miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury

Villena-Rueda,

Kajitani,

Ota

et al. 2024

Mol Neurobiol

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TRP Channels in Excitotoxicity

Zong,

Legere,

Feng

et al. 2024

Neuroscientist

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Glutamate excitotoxicity is a central mechanism contributing to cellular dysfunction and death in various neurological disorders and diseases, such as stroke, traumatic brain injury, epilepsy, schizophrenia, addiction, mood disorders, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, pathologic pain, and even normal aging-related changes. This detrimental effect emerges from glutamate binding to glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, N-methyl-d-aspartate receptors, kainate receptors, and GluD receptors. Thus, excitotoxicity could be prevented by targeting glutamate receptors and their downstream signaling pathways. However, almost all the glutamate receptor antagonists failed to attenuate excitotoxicity in human patients, mainly due to the limited understanding of the underlying mechanisms regulating excitotoxicity. Transient receptor potential (TRP) channels serve as ancient cellular sensors capable of detecting and responding to both external and internal stimuli. The study of human TRP channels has flourished in recent decades since the initial discovery of mammalian TRP in 1995. These channels have been found to play pivotal roles in numerous pathologic conditions, including excitotoxicity. In this review, our focus centers on exploring the intricate interactions between TRP channels and glutamate receptors in excitotoxicity.

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miR-9-5p is downregulated in serum extracellular vesicles of patients treated with biperiden after traumatic brain injury

Villena-Rueda,

Kajitani,

Ota

et al. 2023

Preprint

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Traumatic brain injury (TBI) is a prevalent and debilitating condition, which often leads to the development of post-traumatic epilepsy (PTE), a condition that yet lacks preventive strategies. Biperiden, an anticholinergic drug, is a promising candidate that has shown efficacy in murine models of PTE. MicroRNAs (miRNAs), small regulatory RNAs, can help in understanding the biological basis of PTE, and act as TBI- and PTE-relevant biomarkers that can be detected peripherally, as they are present in extracellular vesicles (EVs) that cross the blood brain barrier. This study aimed to investigate miRNAs in serum EVs from patients with TBI, and their association with biperiden treatment and PTE. Blood samples of 37 TBI patients were collected 10 days after trauma and treatment initiation in a double-blind clinical trial. A total of 18 patients received biperiden, with 3 subjects developing PTE, and 19 received placebo, with 2 developing PTE. Serum EVs were characterized by size distribution and protein profiling, followed by high-throughput sequencing of the EV miRNome. Differential expression analysis revealed no significant differences in miRNA expression between TBI patients with and without PTE. Interestingly, miR-9-5p displayed decreased expression in biperiden-treated patients compared to the placebo group. This miRNA regulates genes enriched in stress response pathways, including axonogenesis and neuronal death, relevant to both PTE and TBI. These findings suggest serum miR-9-5p as a possible marker for biperiden treatment, which may play a role in TBI resolution.

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TRPM4 regulates hilar mossy cell loss in temporal lobe epilepsy

Cited by 3 publications

References 42 publications

miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury

miR-9-5p is Downregulated in Serum Extracellular Vesicles of Patients Treated with Biperiden After Traumatic Brain Injury

TRP Channels in Excitotoxicity

miR-9-5p is downregulated in serum extracellular vesicles of patients treated with biperiden after traumatic brain injury

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