Cargando…
Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression
Numerous studies have examined links between postnatal neurogenesis and depression using a range of experimental methods to deplete neurogenesis. The antimitotic drug temozolomide (TMZ) has previously been used successfully as an experimental tool in animals to deplete adult neurogenesis and is used...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416706/ https://www.ncbi.nlm.nih.gov/pubmed/28440814 http://dx.doi.org/10.1038/tp.2017.68 |
_version_ | 1783233803419910144 |
---|---|
author | Egeland, M Guinaudie, C Du Preez, A Musaelyan, K Zunszain, P A Fernandes, C Pariante, C M Thuret, S |
author_facet | Egeland, M Guinaudie, C Du Preez, A Musaelyan, K Zunszain, P A Fernandes, C Pariante, C M Thuret, S |
author_sort | Egeland, M |
collection | PubMed |
description | Numerous studies have examined links between postnatal neurogenesis and depression using a range of experimental methods to deplete neurogenesis. The antimitotic drug temozolomide (TMZ) has previously been used successfully as an experimental tool in animals to deplete adult neurogenesis and is used regularly on human patients as a standard chemotherapy for brain cancer. In this study, we wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect parameters related to depression in an animal model. Prevalence rates of depression in patients is thought to be highly underdiagnosed, with some studies reporting rates as high as 90%. Results from this study in mice, treated with a regimen of TMZ similar to humans, exhibited behavioural and biochemical changes that have relevance to the development of depression. In particular, behavioural results demonstrated robust deficits in processing novelty and a significant increase in the corticosterone response. Quantification of neurogenesis using a novel sectioning method, which clearly evaluates dorsal and ventral neurogenesis separately, showed a significant correlation between the level of ventral neurogenesis and the corticosterone response. Depression is a complex disorder with discoveries regarding its neurobiology and how it relates to behaviour being only in their infancy. The findings presented in this study demonstrate that chemotherapy-induced decreases in neurogenesis results in previously unreported behavioural and biochemical consequences. These results, we argue, are indicative of a biological mechanism, which may contribute to the development of depression in patients being treated with chemotherapy and is separate from the mental distress resulting from a cancer diagnosis. |
format | Online Article Text |
id | pubmed-5416706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54167062017-05-16 Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression Egeland, M Guinaudie, C Du Preez, A Musaelyan, K Zunszain, P A Fernandes, C Pariante, C M Thuret, S Transl Psychiatry Original Article Numerous studies have examined links between postnatal neurogenesis and depression using a range of experimental methods to deplete neurogenesis. The antimitotic drug temozolomide (TMZ) has previously been used successfully as an experimental tool in animals to deplete adult neurogenesis and is used regularly on human patients as a standard chemotherapy for brain cancer. In this study, we wanted to evaluate whether TMZ as a model for chemotherapy treatment could affect parameters related to depression in an animal model. Prevalence rates of depression in patients is thought to be highly underdiagnosed, with some studies reporting rates as high as 90%. Results from this study in mice, treated with a regimen of TMZ similar to humans, exhibited behavioural and biochemical changes that have relevance to the development of depression. In particular, behavioural results demonstrated robust deficits in processing novelty and a significant increase in the corticosterone response. Quantification of neurogenesis using a novel sectioning method, which clearly evaluates dorsal and ventral neurogenesis separately, showed a significant correlation between the level of ventral neurogenesis and the corticosterone response. Depression is a complex disorder with discoveries regarding its neurobiology and how it relates to behaviour being only in their infancy. The findings presented in this study demonstrate that chemotherapy-induced decreases in neurogenesis results in previously unreported behavioural and biochemical consequences. These results, we argue, are indicative of a biological mechanism, which may contribute to the development of depression in patients being treated with chemotherapy and is separate from the mental distress resulting from a cancer diagnosis. Nature Publishing Group 2017-04 2017-04-25 /pmc/articles/PMC5416706/ /pubmed/28440814 http://dx.doi.org/10.1038/tp.2017.68 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Egeland, M Guinaudie, C Du Preez, A Musaelyan, K Zunszain, P A Fernandes, C Pariante, C M Thuret, S Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title | Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title_full | Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title_fullStr | Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title_full_unstemmed | Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title_short | Depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
title_sort | depletion of adult neurogenesis using the chemotherapy drug temozolomide in mice induces behavioural and biological changes relevant to depression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5416706/ https://www.ncbi.nlm.nih.gov/pubmed/28440814 http://dx.doi.org/10.1038/tp.2017.68 |
work_keys_str_mv | AT egelandm depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT guinaudiec depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT dupreeza depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT musaelyank depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT zunszainpa depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT fernandesc depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT pariantecm depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression AT thurets depletionofadultneurogenesisusingthechemotherapydrugtemozolomideinmiceinducesbehaviouralandbiologicalchangesrelevanttodepression |