Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice
Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wolters Kluwer Medknow Publications
2017-01-01
|
Series: | Neural Regeneration Research |
Subjects: | |
Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=4;spage=588;epage=595;aulast=Neri-Gómez |
id |
doaj-efa0897a281b4bf798e00cba7a4a7440 |
---|---|
record_format |
Article |
spelling |
doaj-efa0897a281b4bf798e00cba7a4a74402020-11-25T03:40:38ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742017-01-0112458859510.4103/1673-5374.205098Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male miceTeresa Neri-GómezJudith Espinosa-RayaSofía Díaz-CintraJulia Segura-UribeSandra Orozco-SuárezJuan Manuel GallardoChristian Guerra-AraizaAging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=4;spage=588;epage=595;aulast=Neri-Gómeznerve regeneration; Tibolone; hippocampus; aged mice; sex steroids; Akt; GSK3β; PI3K; neural plasticity; Tau; neurofibrillary tangles; neural regeneration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Teresa Neri-Gómez Judith Espinosa-Raya Sofía Díaz-Cintra Julia Segura-Uribe Sandra Orozco-Suárez Juan Manuel Gallardo Christian Guerra-Araiza |
spellingShingle |
Teresa Neri-Gómez Judith Espinosa-Raya Sofía Díaz-Cintra Julia Segura-Uribe Sandra Orozco-Suárez Juan Manuel Gallardo Christian Guerra-Araiza Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice Neural Regeneration Research nerve regeneration; Tibolone; hippocampus; aged mice; sex steroids; Akt; GSK3β; PI3K; neural plasticity; Tau; neurofibrillary tangles; neural regeneration |
author_facet |
Teresa Neri-Gómez Judith Espinosa-Raya Sofía Díaz-Cintra Julia Segura-Uribe Sandra Orozco-Suárez Juan Manuel Gallardo Christian Guerra-Araiza |
author_sort |
Teresa Neri-Gómez |
title |
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice |
title_short |
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice |
title_full |
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice |
title_fullStr |
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice |
title_full_unstemmed |
Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice |
title_sort |
tibolone modulates neuronal plasticity through regulating tau, gsk3β/akt/pi3k pathway and cdk5 p35/p25 complexes in the hippocampus of aged male mice |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2017-01-01 |
description |
Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles (NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone (TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB (0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau (PHF-1) proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes. |
topic |
nerve regeneration; Tibolone; hippocampus; aged mice; sex steroids; Akt; GSK3β; PI3K; neural plasticity; Tau; neurofibrillary tangles; neural regeneration |
url |
http://www.nrronline.org/article.asp?issn=1673-5374;year=2017;volume=12;issue=4;spage=588;epage=595;aulast=Neri-Gómez |
work_keys_str_mv |
AT teresanerigomez tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT judithespinosaraya tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT sofiadiazcintra tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT juliasegurauribe tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT sandraorozcosuarez tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT juanmanuelgallardo tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice AT christianguerraaraiza tibolonemodulatesneuronalplasticitythroughregulatingtaugsk3baktpi3kpathwayandcdk5p35p25complexesinthehippocampusofagedmalemice |
_version_ |
1724533756257107968 |