Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment
Abstract Advances in prostate cancer treatment have significantly improved survival, but quality of life for survivors remains an under-studied area of research. Androgen deprivation therapy (ADT) is a foundational treatment for advanced prostate cancer and is used as an adjuvant for prolonged perio...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
|
| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02600-5 |
| _version_ | 1797556243746783232 |
|---|---|
| author | Alexandra M. Vaiana Yidong Chen Jonathan Gelfond Teresa L. Johnson-Pais Robin J. Leach Chethan Ramamurthy Ian M. Thompson David A. Morilak |
| author_facet | Alexandra M. Vaiana Yidong Chen Jonathan Gelfond Teresa L. Johnson-Pais Robin J. Leach Chethan Ramamurthy Ian M. Thompson David A. Morilak |
| author_sort | Alexandra M. Vaiana |
| collection | DOAJ |
| description | Abstract Advances in prostate cancer treatment have significantly improved survival, but quality of life for survivors remains an under-studied area of research. Androgen deprivation therapy (ADT) is a foundational treatment for advanced prostate cancer and is used as an adjuvant for prolonged periods in many high-risk, localized tumors. More than half of patients treated with ADT experience debilitating cognitive impairments in domains such as spatial learning and working memory. In this study, we investigated the effects of androgen deprivation on hippocampal-mediated cognition in rats. Vortioxetine, a multimodal antidepressant, has been shown to improve cognition in depressed patients. Thus, we also tested the potential efficacy of vortioxetine in restoring impaired cognition after ADT. We further investigated mechanisms that might contribute to these effects, measuring changes in the circuitry and gene expression within the dorsal hippocampus. ADT via surgical castration induced impairments in visuospatial cognition on the novel object location test and attenuated afferent-evoked local field potentials recorded in the CA1 region of the dorsal hippocampus. Chronic dietary administration of vortioxetine effectively reversed these deficits. Castration significantly altered gene expression in the hippocampus, whereas vortioxetine had little effect. Pathway analysis revealed that androgen depletion altered pathways related to synaptic plasticity. These results suggest that the hippocampus may be vulnerable to ADT, contributing to cognitive impairment in prostate cancer patients. Further, vortioxetine may be a candidate to improve cognition in patients who experience cognitive decline after androgen deprivation therapy for prostate cancer and may do so by restoring molecular and circuit-level plasticity-related mechanisms compromised by ADT. |
| first_indexed | 2024-03-10T17:00:01Z |
| format | Article |
| id | doaj.art-8d6495592ceb4518a1303cb15fdd755c |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-10T17:00:01Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-8d6495592ceb4518a1303cb15fdd755c2023-11-20T11:00:22ZengNature Publishing GroupTranslational Psychiatry2158-31882023-10-0113111210.1038/s41398-023-02600-5Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatmentAlexandra M. Vaiana0Yidong Chen1Jonathan Gelfond2Teresa L. Johnson-Pais3Robin J. Leach4Chethan Ramamurthy5Ian M. Thompson6David A. Morilak7Department of Pharmacology, University of Texas Health Science CenterGreehey Children’s Cancer Research Institute, University of Texas Health Science CenterDepartment of Population Health Sciences, University of Texas Health Science CenterMays Cancer Center, University of Texas Health Science CenterMays Cancer Center, University of Texas Health Science CenterMays Cancer Center, University of Texas Health Science CenterDepartment of Urology, University of Texas Health Science CenterDepartment of Pharmacology, University of Texas Health Science CenterAbstract Advances in prostate cancer treatment have significantly improved survival, but quality of life for survivors remains an under-studied area of research. Androgen deprivation therapy (ADT) is a foundational treatment for advanced prostate cancer and is used as an adjuvant for prolonged periods in many high-risk, localized tumors. More than half of patients treated with ADT experience debilitating cognitive impairments in domains such as spatial learning and working memory. In this study, we investigated the effects of androgen deprivation on hippocampal-mediated cognition in rats. Vortioxetine, a multimodal antidepressant, has been shown to improve cognition in depressed patients. Thus, we also tested the potential efficacy of vortioxetine in restoring impaired cognition after ADT. We further investigated mechanisms that might contribute to these effects, measuring changes in the circuitry and gene expression within the dorsal hippocampus. ADT via surgical castration induced impairments in visuospatial cognition on the novel object location test and attenuated afferent-evoked local field potentials recorded in the CA1 region of the dorsal hippocampus. Chronic dietary administration of vortioxetine effectively reversed these deficits. Castration significantly altered gene expression in the hippocampus, whereas vortioxetine had little effect. Pathway analysis revealed that androgen depletion altered pathways related to synaptic plasticity. These results suggest that the hippocampus may be vulnerable to ADT, contributing to cognitive impairment in prostate cancer patients. Further, vortioxetine may be a candidate to improve cognition in patients who experience cognitive decline after androgen deprivation therapy for prostate cancer and may do so by restoring molecular and circuit-level plasticity-related mechanisms compromised by ADT.https://doi.org/10.1038/s41398-023-02600-5 |
| spellingShingle | Alexandra M. Vaiana Yidong Chen Jonathan Gelfond Teresa L. Johnson-Pais Robin J. Leach Chethan Ramamurthy Ian M. Thompson David A. Morilak Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment Translational Psychiatry |
| title | Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| title_full | Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| title_fullStr | Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| title_full_unstemmed | Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| title_short | Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| title_sort | effects of vortioxetine on hippocampal related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment |
| url | https://doi.org/10.1038/s41398-023-02600-5 |
| work_keys_str_mv | AT alexandramvaiana effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT yidongchen effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT jonathangelfond effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT teresaljohnsonpais effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT robinjleach effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT chethanramamurthy effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT ianmthompson effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment AT davidamorilak effectsofvortioxetineonhippocampalrelatedcognitiveimpairmentinducedinratsbyandrogendeprivationasamodelofprostatecancertreatment |