The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice
Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mC...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/14/3518 |
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| author | Celeste Nicola Martine Dubois Cynthia Campart Tareq Al Sagheer Laurence Desrues Damien Schapman Ludovic Galas Marie Lange Florence Joly Hélène Castel |
| author_facet | Celeste Nicola Martine Dubois Cynthia Campart Tareq Al Sagheer Laurence Desrues Damien Schapman Ludovic Galas Marie Lange Florence Joly Hélène Castel |
| author_sort | Celeste Nicola |
| collection | DOAJ |
| description | Cognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment were reported. We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ for 5 days per week for six consecutive weeks. ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH<sup>+</sup>-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN<sup>+</sup>-neurons in the dorsal hippocampus. The consequences of the mCRPC treatment ENZ on aged castrated mouse motivation to exploration and cognition should make reconsider management strategy of elderly prostate cancer patients. |
| first_indexed | 2024-03-10T09:43:50Z |
| format | Article |
| id | doaj.art-3324654ee10e4740bfd643cb9cdbab0b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:43:50Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-3324654ee10e4740bfd643cb9cdbab0b2023-11-22T03:24:39ZengMDPI AGCancers2072-66942021-07-011314351810.3390/cancers13143518The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated MiceCeleste Nicola0Martine Dubois1Cynthia Campart2Tareq Al Sagheer3Laurence Desrues4Damien Schapman5Ludovic Galas6Marie Lange7Florence Joly8Hélène Castel9Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceNormandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceNormandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceNormandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceNormandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceInstitute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, FranceInstitute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, FranceCancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, FranceCancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, FranceNormandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, FranceCognitive side effects after cancer treatment threatening quality of life (QoL) constitute a major challenge in oncology. Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are examples of next-generation therapy (NGT) administered to metastatic castration-resistant prostate cancer (mCRPC) patients. NGT significantly improved mCRPC overall survival but neurological side effects such as fatigue and cognitive impairment were reported. We developed a behavioral 17 months-aged and castrated mouse model receiving per os AAP or ENZ for 5 days per week for six consecutive weeks. ENZ exposure reduced spontaneous activity and exploratory behavior associated with a decreased tyrosine hydroxylase (TH)-dopaminergic activity in the substantia nigra pars compacta and the ventral tegmental area. A decrease in TH<sup>+</sup>-DA afferent fibers and Phospho-DARPP32-related dopaminergic neuronal activities in the striatum and the ventral hippocampus highlighted ENZ-induced dopaminergic regulation within the nigrostriatal and mesolimbocortical pathways. ENZ and AAP treatments did not substantially modify spatial learning and memory performances, but ENZ led to a thygmotaxis behavior impacting the cognitive score, and reduced c-fos-related activity of NeuN<sup>+</sup>-neurons in the dorsal hippocampus. The consequences of the mCRPC treatment ENZ on aged castrated mouse motivation to exploration and cognition should make reconsider management strategy of elderly prostate cancer patients.https://www.mdpi.com/2072-6694/13/14/3518metastatic resistant prostate cancerenzalutamideabiraterone acetate/prednisoneaged castrated micebehaviordopaminergic pathways |
| spellingShingle | Celeste Nicola Martine Dubois Cynthia Campart Tareq Al Sagheer Laurence Desrues Damien Schapman Ludovic Galas Marie Lange Florence Joly Hélène Castel The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice Cancers metastatic resistant prostate cancer enzalutamide abiraterone acetate/prednisone aged castrated mice behavior dopaminergic pathways |
| title | The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice |
| title_full | The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice |
| title_fullStr | The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice |
| title_full_unstemmed | The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice |
| title_short | The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice |
| title_sort | prostate cancer therapy enzalutamide compared with abiraterone acetate prednisone impacts motivation for exploration spatial learning and alters dopaminergic transmission in aged castrated mice |
| topic | metastatic resistant prostate cancer enzalutamide abiraterone acetate/prednisone aged castrated mice behavior dopaminergic pathways |
| url | https://www.mdpi.com/2072-6694/13/14/3518 |
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