Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions
The aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexa...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-10-01
|
Series: | Frontiers in Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00756/full |
id |
doaj-32e4b58a2d0d4a66a8de2fc741e0449f |
---|---|
record_format |
Article |
spelling |
doaj-32e4b58a2d0d4a66a8de2fc741e0449f2020-11-24T21:27:41ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-10-011210.3389/fnins.2018.00756417341Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic ConditionsSung Woo Park0Sung Woo Park1Sung Woo Park2Rodrigo B. Mansur3Rodrigo B. Mansur4Yena Lee5Jae-Hon Lee6Mi Kyoung Seo7Ah Jeong Choi8Roger S. McIntyre9Roger S. McIntyre10Roger S. McIntyre11Jung Goo Lee12Jung Goo Lee13Jung Goo Lee14Paik Institute for Clinical Research, Inje University, Busan, South KoreaDepartment of Health Science and Technology, Graduate School, Inje University, Busan, South KoreaDepartment of Convergence Biomedical Science, College of Medicine, Inje University, Busan, South KoreaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Psychiatry, University of Toronto, Toronto, ON, CanadaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Psychiatry, National Rehabilitation Center, Seoul, South KoreaPaik Institute for Clinical Research, Inje University, Busan, South KoreaPaik Institute for Clinical Research, Inje University, Busan, South KoreaMood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, CanadaDepartment of Psychiatry, University of Toronto, Toronto, ON, CanadaDepartment of Pharmacology, University of Toronto, Toronto, ON, CanadaPaik Institute for Clinical Research, Inje University, Busan, South KoreaDepartment of Health Science and Technology, Graduate School, Inje University, Busan, South KoreaDepartment of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan, South KoreaThe aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexamethasone-induced toxic conditions. Western blot analyses were performed to assess changes in mTORC1-mediated proteins, brain-derived neurotrophic factor (BDNF), and various synaptic proteins (PSD-95, synapsin I, and GluA1) in rat hippocampal cultures under toxic conditions induced by dexamethasone, which causes hippocampal cell death. Hippocampal dendritic outgrowth and spine formation were measured using immunostaining procedures. Dexamethasone significantly decreased the phosphorylation levels of mTORC1 as well as its downstream proteins. However, treatment with liraglutide prevented these reductions and significantly increased BDNF expression. The increase in BDNF expression was completely blocked by rapamycin and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Liraglutide also recovered dexamethasone-induced decreases in the total length of hippocampal dendrites and reductions in spine density in a concentration-dependent manner. However, the positive effects of liraglutide on neural plasticity were abolished by the blockade of mTORC1 signaling and AMPA receptors. Furthermore, liraglutide significantly increased the expression levels of PSD-95, synapsin I, and GluA1, whereas rapamycin and NBQX blocked these effects. The present study demonstrated that liraglutide activated mTORC1 signaling and AMPA receptor activity as well as increased dendritic outgrowth, spine density, and synaptic proteins under toxic conditions in rat primary hippocampal neurons. These findings suggest that GLP-1 receptor (GLP-1R) activation by liraglutide may affect neuroplasticity through mTORC1 and AMPA receptors.https://www.frontiersin.org/article/10.3389/fnins.2018.00756/fullmammalian target of rapamycin complex 1 signalingα-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptorglucagon-like peptide 1 receptorliraglutideneuroplasticitytoxic condition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sung Woo Park Sung Woo Park Sung Woo Park Rodrigo B. Mansur Rodrigo B. Mansur Yena Lee Jae-Hon Lee Mi Kyoung Seo Ah Jeong Choi Roger S. McIntyre Roger S. McIntyre Roger S. McIntyre Jung Goo Lee Jung Goo Lee Jung Goo Lee |
spellingShingle |
Sung Woo Park Sung Woo Park Sung Woo Park Rodrigo B. Mansur Rodrigo B. Mansur Yena Lee Jae-Hon Lee Mi Kyoung Seo Ah Jeong Choi Roger S. McIntyre Roger S. McIntyre Roger S. McIntyre Jung Goo Lee Jung Goo Lee Jung Goo Lee Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions Frontiers in Neuroscience mammalian target of rapamycin complex 1 signaling α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor glucagon-like peptide 1 receptor liraglutide neuroplasticity toxic condition |
author_facet |
Sung Woo Park Sung Woo Park Sung Woo Park Rodrigo B. Mansur Rodrigo B. Mansur Yena Lee Jae-Hon Lee Mi Kyoung Seo Ah Jeong Choi Roger S. McIntyre Roger S. McIntyre Roger S. McIntyre Jung Goo Lee Jung Goo Lee Jung Goo Lee |
author_sort |
Sung Woo Park |
title |
Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions |
title_short |
Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions |
title_full |
Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions |
title_fullStr |
Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions |
title_full_unstemmed |
Liraglutide Activates mTORC1 Signaling and AMPA Receptors in Rat Hippocampal Neurons Under Toxic Conditions |
title_sort |
liraglutide activates mtorc1 signaling and ampa receptors in rat hippocampal neurons under toxic conditions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-10-01 |
description |
The aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexamethasone-induced toxic conditions. Western blot analyses were performed to assess changes in mTORC1-mediated proteins, brain-derived neurotrophic factor (BDNF), and various synaptic proteins (PSD-95, synapsin I, and GluA1) in rat hippocampal cultures under toxic conditions induced by dexamethasone, which causes hippocampal cell death. Hippocampal dendritic outgrowth and spine formation were measured using immunostaining procedures. Dexamethasone significantly decreased the phosphorylation levels of mTORC1 as well as its downstream proteins. However, treatment with liraglutide prevented these reductions and significantly increased BDNF expression. The increase in BDNF expression was completely blocked by rapamycin and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Liraglutide also recovered dexamethasone-induced decreases in the total length of hippocampal dendrites and reductions in spine density in a concentration-dependent manner. However, the positive effects of liraglutide on neural plasticity were abolished by the blockade of mTORC1 signaling and AMPA receptors. Furthermore, liraglutide significantly increased the expression levels of PSD-95, synapsin I, and GluA1, whereas rapamycin and NBQX blocked these effects. The present study demonstrated that liraglutide activated mTORC1 signaling and AMPA receptor activity as well as increased dendritic outgrowth, spine density, and synaptic proteins under toxic conditions in rat primary hippocampal neurons. These findings suggest that GLP-1 receptor (GLP-1R) activation by liraglutide may affect neuroplasticity through mTORC1 and AMPA receptors. |
topic |
mammalian target of rapamycin complex 1 signaling α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor glucagon-like peptide 1 receptor liraglutide neuroplasticity toxic condition |
url |
https://www.frontiersin.org/article/10.3389/fnins.2018.00756/full |
work_keys_str_mv |
AT sungwoopark liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT sungwoopark liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT sungwoopark liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT rodrigobmansur liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT rodrigobmansur liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT yenalee liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT jaehonlee liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT mikyoungseo liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT ahjeongchoi liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT rogersmcintyre liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT rogersmcintyre liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT rogersmcintyre liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT junggoolee liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT junggoolee liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions AT junggoolee liraglutideactivatesmtorc1signalingandampareceptorsinrathippocampalneuronsundertoxicconditions |
_version_ |
1725973970457460736 |