The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/46303 |
Resumo: | Copyright © 2020 Belo, Martins, Shvachiy, Costa-Coelho, de Almeida-Borlido, Fonseca-Gomes, Neves, Vicente Miranda, Outeiro, Coelho, Xapelli, Valente, Heras, Bardaji, Castanho, Diogenes and Sebastião. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiologyAmidated-kyotorphinAlzheimer’s diseaseAmyloid b peptideNovel object recognition testY-Maze alternation testLong-term potentiationMemorySynaptic plasticityCopyright © 2020 Belo, Martins, Shvachiy, Costa-Coelho, de Almeida-Borlido, Fonseca-Gomes, Neves, Vicente Miranda, Outeiro, Coelho, Xapelli, Valente, Heras, Bardaji, Castanho, Diogenes and Sebastião. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer's disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH2, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH2 treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH2, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH2. Co-incubation with KTP-NH2 (50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH2 (50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH2 treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.This study was supported by Santa Casa da Misericórdia de Lisboa (MB37-2017) and Fundação para a Ciência e Tecnologia (FCT): PTDC/NEU-OSD/5644/2014, and PTDC/BIA-VIR/29495/2017. RFB was supported by FCT (PD/BD/114337/2016). JF-G was supported by FCT (PD/BD/114441/2016). JEC was supported by FCT (SFRH/BPD/87647/2012).FrontiersRepositório da Universidade de LisboaBelo, Rita F.Martins, Margarida L. F.Shvachiy, LianaCosta-Coelho, Tiagode Almeida-Borlido, CarolinaFonseca-Gomes, JoãoNeves, VeraVicente Miranda, HugoOuteiro, Tiago F.Coelho, Joana EXapelli, SaraValente, Cláudia A.Heras, MontserratBardaji, EduardCastanho, Miguel A. R. B.Diógenes, Maria JoséSebastião, Ana M2021-02-12T17:17:34Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/46303engFront Pharmacol. 2020 Jul 9;11:985.10.3389/fphar.2020.009851663-9812info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:48:33Zoai:repositorio.ul.pt:10451/46303Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:58:32.458288Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| title |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| spellingShingle |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology Belo, Rita F. Amidated-kyotorphin Alzheimer’s disease Amyloid b peptide Novel object recognition test Y-Maze alternation test Long-term potentiation Memory Synaptic plasticity |
| title_short |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| title_full |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| title_fullStr |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| title_full_unstemmed |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| title_sort |
The neuroprotective action of amidated-kyotorphin on amyloid β peptide-induced Alzheimer’s disease pathophysiology |
| author |
Belo, Rita F. |
| author_facet |
Belo, Rita F. Martins, Margarida L. F. Shvachiy, Liana Costa-Coelho, Tiago de Almeida-Borlido, Carolina Fonseca-Gomes, João Neves, Vera Vicente Miranda, Hugo Outeiro, Tiago F. Coelho, Joana E Xapelli, Sara Valente, Cláudia A. Heras, Montserrat Bardaji, Eduard Castanho, Miguel A. R. B. Diógenes, Maria José Sebastião, Ana M |
| author_role |
author |
| author2 |
Martins, Margarida L. F. Shvachiy, Liana Costa-Coelho, Tiago de Almeida-Borlido, Carolina Fonseca-Gomes, João Neves, Vera Vicente Miranda, Hugo Outeiro, Tiago F. Coelho, Joana E Xapelli, Sara Valente, Cláudia A. Heras, Montserrat Bardaji, Eduard Castanho, Miguel A. R. B. Diógenes, Maria José Sebastião, Ana M |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Belo, Rita F. Martins, Margarida L. F. Shvachiy, Liana Costa-Coelho, Tiago de Almeida-Borlido, Carolina Fonseca-Gomes, João Neves, Vera Vicente Miranda, Hugo Outeiro, Tiago F. Coelho, Joana E Xapelli, Sara Valente, Cláudia A. Heras, Montserrat Bardaji, Eduard Castanho, Miguel A. R. B. Diógenes, Maria José Sebastião, Ana M |
| dc.subject.por.fl_str_mv |
Amidated-kyotorphin Alzheimer’s disease Amyloid b peptide Novel object recognition test Y-Maze alternation test Long-term potentiation Memory Synaptic plasticity |
| topic |
Amidated-kyotorphin Alzheimer’s disease Amyloid b peptide Novel object recognition test Y-Maze alternation test Long-term potentiation Memory Synaptic plasticity |
| description |
Copyright © 2020 Belo, Martins, Shvachiy, Costa-Coelho, de Almeida-Borlido, Fonseca-Gomes, Neves, Vicente Miranda, Outeiro, Coelho, Xapelli, Valente, Heras, Bardaji, Castanho, Diogenes and Sebastião. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-02-12T17:17:34Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/46303 |
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http://hdl.handle.net/10451/46303 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Front Pharmacol. 2020 Jul 9;11:985. 10.3389/fphar.2020.00985 1663-9812 |
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Frontiers |
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Frontiers |
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