Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate...

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Published in:Biomedicine and Pharmacotherapy
Main Author: Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
Format: Article
Language:English
Published: Elsevier Masson SAS 2019
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056751798&doi=10.1016%2fj.biopha.2018.11.044&partnerID=40&md5=73382c07656c218a61c137f173b983fd
id 2-s2.0-85056751798
spelling 2-s2.0-85056751798
Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
2019
Biomedicine and Pharmacotherapy
110

10.1016/j.biopha.2018.11.044
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056751798&doi=10.1016%2fj.biopha.2018.11.044&partnerID=40&md5=73382c07656c218a61c137f173b983fd
Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABA A receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression. © 2018 The Authors
Elsevier Masson SAS
7533322
English
Article
All Open Access; Gold Open Access
author Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
spellingShingle Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
author_facet Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
author_sort Wong J.H.; Muthuraju S.; Reza F.; Senik M.H.; Zhang J.; Mohd Yusuf Yeo N.A.B.; Chuang H.G.; Jaafar H.; Yusof S.R.; Mohamad H.; Tengku Muhammad T.S.; Ismail N.H.; Husin S.S.; Abdullah J.M.
title Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
title_short Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
title_full Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
title_fullStr Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
title_full_unstemmed Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
title_sort Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica
publishDate 2019
container_title Biomedicine and Pharmacotherapy
container_volume 110
container_issue
doi_str_mv 10.1016/j.biopha.2018.11.044
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85056751798&doi=10.1016%2fj.biopha.2018.11.044&partnerID=40&md5=73382c07656c218a61c137f173b983fd
description Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABA A receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression. © 2018 The Authors
publisher Elsevier Masson SAS
issn 7533322
language English
format Article
accesstype All Open Access; Gold Open Access
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