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The Glucagon-Like P...
The Glucagon-Like Peptide-1 Analogue Liraglutide Reduces Seizures Susceptibility, Cognition Dysfunction and Neuronal Apoptosis in a Mouse Model of Dravet Syndrome
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- Liu, Shenhai (author)
- 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 China
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- Jin, Zhe (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi,Ningxia Med Univ, Ningxia Key Lab Cerebrocranial Dis, Incubat Base Natl Key Lab, Yinchuan, Ningxia, Peoples R China
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- Zhang, Yiling (author)
- HuBei Univ Med, Affiliated DongFeng Hosp, Dept Integrated Med, Shiyan, Peoples R China
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- Rong, ShiKuo (author)
- 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 China
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- He, Wenxin (author)
- 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 China
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- Sun, Kuisheng (author)
- 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 China
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- Wan, Din (author)
- 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 China
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- Huo, Junming (author)
- 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 China
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- Xiao, Lifei (author)
- 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 China
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- Li, Xinxiao (author)
- 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 China
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- Ding, Na (author)
- 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 China
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- Wang, Feng (author)
- 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 China
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- Sun, Tao (author)
- 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 China
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(creator_code:org_t)
- 2020-02-28
- 2020
- English.
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- apoptosis
- Dravet syndrome
- epilepsy
- GLP-1
- mTOR
- neuroprotection
- SCN1A
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Liu, Shenhai
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Jin, Zhe
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Zhang, Yiling
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Rong, ShiKuo
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He, Wenxin
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Sun, Kuisheng
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show more...
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Wan, Din
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Huo, Junming
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Xiao, Lifei
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Li, Xinxiao
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Ding, Na
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Wang, Feng
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Sun, Tao
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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Frontiers in Pha ...
- By the university
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Uppsala University