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Sökning: id:"swepub:oai:DiVA.org:uu-410144" > The Glucagon-Like P...

  • Liu, ShenhaiNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)

The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • 2020-02-28
  • Frontiers Media SA,2020
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-410144
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-410144URI
  • https://doi.org/10.3389/fphar.2020.00136DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Dravet syndrome (DS) is a refractory epilepsy typically caused by heterozygous mutations of the Scn1a gene, which encodes the voltage-gated sodium channel Nav1.1. Glucagon-like peptide-1 (GLP-1) analogues, effective therapeutic agents for the treatment of diabetes, have recently become attractive treatment modalities for patients with nervous system disease; however, the impact of GLP-1 analogues on DS remains unknown. This study aimed to determine the neuroprotective role of liraglutide in mouse and cell models of Scn1a KO-induced epilepsy. Epileptic susceptibility, behavioral changes, and behavioral seizures were assessed using electroencephalography (EEG), IntelliCage (TSE Systems, Bad Homburg, Germany), and the open field task. Morphological changes in brain tissues were observed using hematoxylin and eosin (HE) and Nissl staining. Expression of apoptosis-related proteins and the mammalian target of rapamycin (mTOR) signaling pathway were determined using immunofluorescence and western blotting in Scn1a KO-induced epileptic mice in vitro. Scn1a KO model cell proliferation was evaluated using the Cell Counting Kit-8 assay, and the effect of liraglutide on cellular apoptosis levels was examined using Annexin V-FITC/PI flow cytometry. Apoptotic signal proteins and mTOR were assessed using reverse transcription - quantitative polymerase chain reaction (RT-qPCR) and western blotting. Our results showed that liraglutide significantly increased mRNA ((0.31 ± 0.04) *10-3 vs. (1.07 ± 0.08) * 10-3, P = 0.0004) and protein (0.10 ± 0.02 vs. 0.27 ± 0.02, P = 0.0006) expression of Scn1a in Scn1a KO-induced epileptic mice. In addition, liraglutide significantly alleviated electroencephalographic seizures, the severity of responses to epileptic seizures (96.53 ± 0.45 % vs. 85.98 ± 1.24 %, P = 0.0003), cognitive dysfunction, and epileptic-related necrotic neurons (9.76 ± 0.91 % vs. 19.65 ± 2.64 %, P = 0.0005) in Scn1a KO-induced epileptic mice. Moreover, liraglutide protected against Scn1a KO-induced apoptosis, which was manifested in the phosphorylation of mTOR (KO+NS: 1.99 ± 0.31 vs. KO+Lira: 0.97 ± 0.18, P = 0.0004), as well as the downregulation of cleaved caspase-3 (KO+NS: 0.49 ± 0.04 vs. KO+Lira: 0.30 ± 0.01, P = 0.0003) and restoration of the imbalance between BAX (KO+NS: 0.90 ± 0.02 vs. KO+Lira: 0.75 ± 0.04, P = 0.0005) and BCL-2 (KO+NS: 0.46 ± 0.02 vs. KO+Lira: 0.61 ± 0.02, P = 0.0006). Collectively, these results show that liraglutide reduces seizure susceptibility and cognitive dysfunction in the mouse model of Dravet syndrome, and exerts anti-apoptotic and neuroprotective effects in Scn1a KO mice and cells.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Jin, ZheUppsala universitet,Institutionen för medicinsk cellbiologi,Ningxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China(Swepub:uu)zheji315 (författare)
  • Zhang, YilingHuBei Univ Med, Affiliated DongFeng Hosp, Dept Integrated Med, Shiyan, Peoples R China (författare)
  • Rong, ShiKuoNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • He, WenxinNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Sun, KuishengNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Wan, DinNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Huo, JunmingNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Xiao, LifeiNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Li, XinxiaoNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China.;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Ding, NaNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Wang, FengNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Sun, TaoNingxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R China (författare)
  • Ningxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China;Ningxia Med Univ, Dept Neurosurg, Gen Hosp, Yinchuan, Ningxia, Peoples R ChinaInstitutionen för medicinsk cellbiologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Frontiers in Pharmacology: Frontiers Media SA111663-9812

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