Eintrag weiter verarbeiten
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transg...
Gespeichert in:
| Zeitschriftentitel: | International Journal of Neuropsychopharmacology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | International Journal of Neuropsychopharmacology, 23, 2020, 10, S. 700-711 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Oxford University Press (OUP)
|
| Schlagwörter: |
| author_facet |
Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting |
|---|---|
| author |
Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting |
| spellingShingle |
Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting International Journal of Neuropsychopharmacology The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice Pharmacology (medical) Psychiatry and Mental health Pharmacology |
| author_sort |
wang, hao |
| spelling |
Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting 1461-1457 1469-5111 Oxford University Press (OUP) Pharmacology (medical) Psychiatry and Mental health Pharmacology http://dx.doi.org/10.1093/ijnp/pyaa048 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Depression is highly related to Alzheimer’s disease (AD), yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinical use, improves cognition at doses that do not cause side effects such as emesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we examined the effects of roflumilast on behavioral dysfunction and the related mechanisms in APPswe/PS1dE9 transgenic mice, a widely used model of AD. Mice at 10 months of age were examined for memory in the novel object recognition and Morris water-maze tests and depression-like behavior in the tail-suspension test and forced swimming test before killing for neurochemical assays.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the novel object recognition and Morris water-maze, APPswe/PS1dE9 mice showed significant cognitive declines, which were reversed by roflumilast at 5 and 10 mg/kg orally once per day. In the tail-suspension test and forced swimming test, the AD mice showed prolonged immobility time, which was also reversed by roflumilast. In addition, the staining of hematoxylin–eosin and Nissl showed that roflumilast relieved the neuronal cell injuries, while terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling analysis indicated that roflumilast ameliorated cell apoptosis in AD mice. Further, roflumilast reversed the decreased ratio of B-cell lymphoma-2/Bcl-2-associated X protein and the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of AD mice. Finally, roflumilast reversed the decreased levels of cyclic AMP (cAMP) and expression of phosphorylated cAMP response element-binding protein and brain derived neurotrophic factor in AD mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Together, these results suggest that roflumilast not only improves learning and memory but also attenuates depression-like behavior in AD mice, likely via PDE4B/PDE4D-mediated cAMP/cAMP response element-binding protein/brain derived neurotrophic factor signaling. Roflumilast can be a therapeutic agent for AD, in particular the comorbidity of memory loss and depression.</jats:p> </jats:sec> The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice International Journal of Neuropsychopharmacology |
| doi_str_mv |
10.1093/ijnp/pyaa048 |
| facet_avail |
Online Free |
| finc_class_facet |
Chemie und Pharmazie Medizin Psychologie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5My9pam5wL3B5YWEwNDg |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5My9pam5wL3B5YWEwNDg |
| institution |
DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 |
| imprint |
Oxford University Press (OUP), 2020 |
| imprint_str_mv |
Oxford University Press (OUP), 2020 |
| issn |
1469-5111 1461-1457 |
| issn_str_mv |
1469-5111 1461-1457 |
| language |
English |
| mega_collection |
Oxford University Press (OUP) (CrossRef) |
| match_str |
wang2020thephosphodiesterase4inhibitorroflumilastapotentialtreatmentforthecomorbidityofmemorylossanddepressioninalzheimersdiseaseapreclinicalstudyinappps1transgenicmice |
| publishDateSort |
2020 |
| publisher |
Oxford University Press (OUP) |
| recordtype |
ai |
| record_format |
ai |
| series |
International Journal of Neuropsychopharmacology |
| source_id |
49 |
| title |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_unstemmed |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_full |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_fullStr |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_full_unstemmed |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_short |
The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_sort |
the phosphodiesterase-4 inhibitor roflumilast, a potential treatment for the comorbidity of memory loss and depression in alzheimer’s disease: a preclinical study in app/ps1 transgenic mice |
| topic |
Pharmacology (medical) Psychiatry and Mental health Pharmacology |
| url |
http://dx.doi.org/10.1093/ijnp/pyaa048 |
| publishDate |
2020 |
| physical |
700-711 |
| description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Depression is highly related to Alzheimer’s disease (AD), yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinical use, improves cognition at doses that do not cause side effects such as emesis.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Here we examined the effects of roflumilast on behavioral dysfunction and the related mechanisms in APPswe/PS1dE9 transgenic mice, a widely used model of AD. Mice at 10 months of age were examined for memory in the novel object recognition and Morris water-maze tests and depression-like behavior in the tail-suspension test and forced swimming test before killing for neurochemical assays.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>In the novel object recognition and Morris water-maze, APPswe/PS1dE9 mice showed significant cognitive declines, which were reversed by roflumilast at 5 and 10 mg/kg orally once per day. In the tail-suspension test and forced swimming test, the AD mice showed prolonged immobility time, which was also reversed by roflumilast. In addition, the staining of hematoxylin–eosin and Nissl showed that roflumilast relieved the neuronal cell injuries, while terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling analysis indicated that roflumilast ameliorated cell apoptosis in AD mice. Further, roflumilast reversed the decreased ratio of B-cell lymphoma-2/Bcl-2-associated X protein and the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of AD mice. Finally, roflumilast reversed the decreased levels of cyclic AMP (cAMP) and expression of phosphorylated cAMP response element-binding protein and brain derived neurotrophic factor in AD mice.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Together, these results suggest that roflumilast not only improves learning and memory but also attenuates depression-like behavior in AD mice, likely via PDE4B/PDE4D-mediated cAMP/cAMP response element-binding protein/brain derived neurotrophic factor signaling. Roflumilast can be a therapeutic agent for AD, in particular the comorbidity of memory loss and depression.</jats:p>
</jats:sec> |
| container_issue |
10 |
| container_start_page |
700 |
| container_title |
International Journal of Neuropsychopharmacology |
| container_volume |
23 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792348581084004354 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T18:13:26.929Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=The+Phosphodiesterase-4+Inhibitor+Roflumilast%2C+a+Potential+Treatment+for+the+Comorbidity+of+Memory+Loss+and+Depression+in+Alzheimer%E2%80%99s+Disease%3A+A+Preclinical+Study+in+APP%2FPS1+Transgenic+Mice&rft.date=2020-12-10&genre=article&issn=1469-5111&volume=23&issue=10&spage=700&epage=711&pages=700-711&jtitle=International+Journal+of+Neuropsychopharmacology&atitle=The+Phosphodiesterase-4+Inhibitor+Roflumilast%2C+a+Potential+Treatment+for+the+Comorbidity+of+Memory+Loss+and+Depression+in+Alzheimer%E2%80%99s+Disease%3A+A+Preclinical+Study+in+APP%2FPS1+Transgenic+Mice&aulast=Zhang&aufirst=Han-Ting&rft_id=info%3Adoi%2F10.1093%2Fijnp%2Fpyaa048&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792348581084004354 |
| author | Wang, Hao, Zhang, Fang-fang, Xu, Yong, Fu, Hua-rong, Wang, Xiao-dan, Wang, Lei, Chen, Wei, Xu, Xiao-yan, Gao, Yong-feng, Zhang, Ji-guo, Zhang, Han-Ting |
| author_facet | Wang, Hao, Zhang, Fang-fang, Xu, Yong, Fu, Hua-rong, Wang, Xiao-dan, Wang, Lei, Chen, Wei, Xu, Xiao-yan, Gao, Yong-feng, Zhang, Ji-guo, Zhang, Han-Ting, Wang, Hao, Zhang, Fang-fang, Xu, Yong, Fu, Hua-rong, Wang, Xiao-dan, Wang, Lei, Chen, Wei, Xu, Xiao-yan, Gao, Yong-feng, Zhang, Ji-guo, Zhang, Han-Ting |
| author_sort | wang, hao |
| container_issue | 10 |
| container_start_page | 700 |
| container_title | International Journal of Neuropsychopharmacology |
| container_volume | 23 |
| description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Depression is highly related to Alzheimer’s disease (AD), yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinical use, improves cognition at doses that do not cause side effects such as emesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we examined the effects of roflumilast on behavioral dysfunction and the related mechanisms in APPswe/PS1dE9 transgenic mice, a widely used model of AD. Mice at 10 months of age were examined for memory in the novel object recognition and Morris water-maze tests and depression-like behavior in the tail-suspension test and forced swimming test before killing for neurochemical assays.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the novel object recognition and Morris water-maze, APPswe/PS1dE9 mice showed significant cognitive declines, which were reversed by roflumilast at 5 and 10 mg/kg orally once per day. In the tail-suspension test and forced swimming test, the AD mice showed prolonged immobility time, which was also reversed by roflumilast. In addition, the staining of hematoxylin–eosin and Nissl showed that roflumilast relieved the neuronal cell injuries, while terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling analysis indicated that roflumilast ameliorated cell apoptosis in AD mice. Further, roflumilast reversed the decreased ratio of B-cell lymphoma-2/Bcl-2-associated X protein and the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of AD mice. Finally, roflumilast reversed the decreased levels of cyclic AMP (cAMP) and expression of phosphorylated cAMP response element-binding protein and brain derived neurotrophic factor in AD mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Together, these results suggest that roflumilast not only improves learning and memory but also attenuates depression-like behavior in AD mice, likely via PDE4B/PDE4D-mediated cAMP/cAMP response element-binding protein/brain derived neurotrophic factor signaling. Roflumilast can be a therapeutic agent for AD, in particular the comorbidity of memory loss and depression.</jats:p> </jats:sec> |
| doi_str_mv | 10.1093/ijnp/pyaa048 |
| facet_avail | Online, Free |
| finc_class_facet | Chemie und Pharmazie, Medizin, Psychologie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTA5My9pam5wL3B5YWEwNDg |
| imprint | Oxford University Press (OUP), 2020 |
| imprint_str_mv | Oxford University Press (OUP), 2020 |
| institution | DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275 |
| issn | 1469-5111, 1461-1457 |
| issn_str_mv | 1469-5111, 1461-1457 |
| language | English |
| last_indexed | 2024-03-01T18:13:26.929Z |
| match_str | wang2020thephosphodiesterase4inhibitorroflumilastapotentialtreatmentforthecomorbidityofmemorylossanddepressioninalzheimersdiseaseapreclinicalstudyinappps1transgenicmice |
| mega_collection | Oxford University Press (OUP) (CrossRef) |
| physical | 700-711 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Oxford University Press (OUP) |
| record_format | ai |
| recordtype | ai |
| series | International Journal of Neuropsychopharmacology |
| source_id | 49 |
| spelling | Wang, Hao Zhang, Fang-fang Xu, Yong Fu, Hua-rong Wang, Xiao-dan Wang, Lei Chen, Wei Xu, Xiao-yan Gao, Yong-feng Zhang, Ji-guo Zhang, Han-Ting 1461-1457 1469-5111 Oxford University Press (OUP) Pharmacology (medical) Psychiatry and Mental health Pharmacology http://dx.doi.org/10.1093/ijnp/pyaa048 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Depression is highly related to Alzheimer’s disease (AD), yet no effective treatment is available. Phosphodiesterase-4 (PDE4) has been considered a promising target for treatment of AD and depression. Roflumilast, the first PDE4 inhibitor approved for clinical use, improves cognition at doses that do not cause side effects such as emesis.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Here we examined the effects of roflumilast on behavioral dysfunction and the related mechanisms in APPswe/PS1dE9 transgenic mice, a widely used model of AD. Mice at 10 months of age were examined for memory in the novel object recognition and Morris water-maze tests and depression-like behavior in the tail-suspension test and forced swimming test before killing for neurochemical assays.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In the novel object recognition and Morris water-maze, APPswe/PS1dE9 mice showed significant cognitive declines, which were reversed by roflumilast at 5 and 10 mg/kg orally once per day. In the tail-suspension test and forced swimming test, the AD mice showed prolonged immobility time, which was also reversed by roflumilast. In addition, the staining of hematoxylin–eosin and Nissl showed that roflumilast relieved the neuronal cell injuries, while terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling analysis indicated that roflumilast ameliorated cell apoptosis in AD mice. Further, roflumilast reversed the decreased ratio of B-cell lymphoma-2/Bcl-2-associated X protein and the increased expression of PDE4B and PDE4D in the cerebral cortex and hippocampus of AD mice. Finally, roflumilast reversed the decreased levels of cyclic AMP (cAMP) and expression of phosphorylated cAMP response element-binding protein and brain derived neurotrophic factor in AD mice.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Together, these results suggest that roflumilast not only improves learning and memory but also attenuates depression-like behavior in AD mice, likely via PDE4B/PDE4D-mediated cAMP/cAMP response element-binding protein/brain derived neurotrophic factor signaling. Roflumilast can be a therapeutic agent for AD, in particular the comorbidity of memory loss and depression.</jats:p> </jats:sec> The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice International Journal of Neuropsychopharmacology |
| spellingShingle | Wang, Hao, Zhang, Fang-fang, Xu, Yong, Fu, Hua-rong, Wang, Xiao-dan, Wang, Lei, Chen, Wei, Xu, Xiao-yan, Gao, Yong-feng, Zhang, Ji-guo, Zhang, Han-Ting, International Journal of Neuropsychopharmacology, The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice, Pharmacology (medical), Psychiatry and Mental health, Pharmacology |
| title | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_full | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_fullStr | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_full_unstemmed | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_short | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| title_sort | the phosphodiesterase-4 inhibitor roflumilast, a potential treatment for the comorbidity of memory loss and depression in alzheimer’s disease: a preclinical study in app/ps1 transgenic mice |
| title_unstemmed | The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer’s Disease: A Preclinical Study in APP/PS1 Transgenic Mice |
| topic | Pharmacology (medical), Psychiatry and Mental health, Pharmacology |
| url | http://dx.doi.org/10.1093/ijnp/pyaa048 |