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The Prostate Cancer Therapy Enzalutamide Compared with Abiraterone Acetate/Prednisone Impacts Motivation for Exploration, Spatial Learning and Alters Dopaminergic Transmission in Aged Castrated Mice.
Nicola, Celeste; Dubois, Martine; Campart, Cynthia; Al Sagheer, Tareq; Desrues, Laurence; Schapman, Damien; Galas, Ludovic; Lange, Marie; Joly, Florence; Castel, Hélène.
Affiliation
  • Nicola C; Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, France.
  • Dubois M; Institute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, France.
  • Campart C; Cancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, France.
  • Al Sagheer T; Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, France.
  • Desrues L; Institute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, France.
  • Schapman D; Cancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, France.
  • Galas L; Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, France.
  • Lange M; Institute for Research and Innovation in Biomedicine (IRIB), 76000 Rouen, France.
  • Joly F; Cancer and Cognition Platform, Ligue Nationale contre le Cancer, 14000 Caen, France.
  • Castel H; Normandie University, UNIROUEN, INSERM, U1239 DC2N, 76000 Rouen, France.
Cancers (Basel) ; 13(14)2021 Jul 14.
Article in En | MEDLINE | ID: mdl-34298734
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+-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+-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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Aspects: Patient_preference Language: En Journal: Cancers (Basel) Year: 2021 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Aspects: Patient_preference Language: En Journal: Cancers (Basel) Year: 2021 Document type: Article Affiliation country: Country of publication: