Cargando…
Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse
No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tr...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617346/ https://www.ncbi.nlm.nih.gov/pubmed/31174258 http://dx.doi.org/10.3390/antiox8060163 |
_version_ | 1783433671657652224 |
---|---|
author | Giacomini, Andrea Stagni, Fiorenza Emili, Marco Uguagliati, Beatrice Rimondini, Roberto Bartesaghi, Renata Guidi, Sandra |
author_facet | Giacomini, Andrea Stagni, Fiorenza Emili, Marco Uguagliati, Beatrice Rimondini, Roberto Bartesaghi, Renata Guidi, Sandra |
author_sort | Giacomini, Andrea |
collection | PubMed |
description | No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. Based on previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. Based on evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain. |
format | Online Article Text |
id | pubmed-6617346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66173462019-07-18 Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse Giacomini, Andrea Stagni, Fiorenza Emili, Marco Uguagliati, Beatrice Rimondini, Roberto Bartesaghi, Renata Guidi, Sandra Antioxidants (Basel) Communication No therapies currently exist for intellectual disability in Down syndrome (DS). In view of its similarities with DS, including learning and memory (L&M) defects, the Ts65Dn mouse model of DS is widely used for the design of therapy. 7,8-dihydroxyflavone (7,8-DHF), a flavonoid that targets the tropomyosin-related kinase B (TrkB) receptor of brain-derived neurotrophic factor (BDNF), exerts positive effects in various brain disease models. Based on previous demonstration that administration of 7,8-DHF in the postnatal period P3-P15 restores hippocampal neurogenesis and spinogenesis, we sought to establish whether these effects translate into behavioral benefits after treatment cessation. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) during postnatal days P3-P15 did not show any L&M improvement at one month after treatment cessation, indicating that the effects of 7,8-DHF on the brain are ephemeral. Based on evidence that chronic treatment with 7,8-DHF in juvenile Ts65Dn mice restores L&M, we sought to establish whether a similar effect is elicited in adulthood. We found that Ts65Dn mice treated with 7,8-DHF (5.0 mg/kg/day) for about 40 days starting from 4 months of age did not show any improvement in L&M. The results suggest that timing of therapy with 7,8-DHF is a critical issue for attainment of positive effects on the brain. MDPI 2019-06-06 /pmc/articles/PMC6617346/ /pubmed/31174258 http://dx.doi.org/10.3390/antiox8060163 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Giacomini, Andrea Stagni, Fiorenza Emili, Marco Uguagliati, Beatrice Rimondini, Roberto Bartesaghi, Renata Guidi, Sandra Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title | Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title_full | Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title_fullStr | Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title_full_unstemmed | Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title_short | Timing of Treatment with the Flavonoid 7,8-DHF Critically Impacts on Its Effects on Learning and Memory in the Ts65Dn Mouse |
title_sort | timing of treatment with the flavonoid 7,8-dhf critically impacts on its effects on learning and memory in the ts65dn mouse |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617346/ https://www.ncbi.nlm.nih.gov/pubmed/31174258 http://dx.doi.org/10.3390/antiox8060163 |
work_keys_str_mv | AT giacominiandrea timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT stagnifiorenza timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT emilimarco timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT uguagliatibeatrice timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT rimondiniroberto timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT bartesaghirenata timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse AT guidisandra timingoftreatmentwiththeflavonoid78dhfcriticallyimpactsonitseffectsonlearningandmemoryinthets65dnmouse |