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Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss

Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analyse...

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Autores principales: Vukmanovic Nosrat, Irina, Palacios, Jerry L., Kezian, Steven, Luong, Gloria, Tran, Andrew, Vu, Kim, Henson, Bradley S., Nosrat, Philip, Lutfy, Kabirullah, Nosrat, Christopher A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804163/
https://www.ncbi.nlm.nih.gov/pubmed/35986485
http://dx.doi.org/10.1111/ejn.15799
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author Vukmanovic Nosrat, Irina
Palacios, Jerry L.
Kezian, Steven
Luong, Gloria
Tran, Andrew
Vu, Kim
Henson, Bradley S.
Nosrat, Philip
Lutfy, Kabirullah
Nosrat, Christopher A.
author_facet Vukmanovic Nosrat, Irina
Palacios, Jerry L.
Kezian, Steven
Luong, Gloria
Tran, Andrew
Vu, Kim
Henson, Bradley S.
Nosrat, Philip
Lutfy, Kabirullah
Nosrat, Christopher A.
author_sort Vukmanovic Nosrat, Irina
collection PubMed
description Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain‐derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle‐treated wild‐type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild‐type mice caused total taste loss. Gustducin‐BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild‐type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug‐treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.
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spelling pubmed-98041632023-01-03 Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss Vukmanovic Nosrat, Irina Palacios, Jerry L. Kezian, Steven Luong, Gloria Tran, Andrew Vu, Kim Henson, Bradley S. Nosrat, Philip Lutfy, Kabirullah Nosrat, Christopher A. Eur J Neurosci Molecular and Synaptic Mechanisms Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain‐derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle‐treated wild‐type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild‐type mice caused total taste loss. Gustducin‐BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild‐type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug‐treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC. John Wiley and Sons Inc. 2022-08-31 2022-10 /pmc/articles/PMC9804163/ /pubmed/35986485 http://dx.doi.org/10.1111/ejn.15799 Text en © 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular and Synaptic Mechanisms
Vukmanovic Nosrat, Irina
Palacios, Jerry L.
Kezian, Steven
Luong, Gloria
Tran, Andrew
Vu, Kim
Henson, Bradley S.
Nosrat, Philip
Lutfy, Kabirullah
Nosrat, Christopher A.
Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title_full Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title_fullStr Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title_full_unstemmed Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title_short Brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
title_sort brain‐derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss
topic Molecular and Synaptic Mechanisms
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804163/
https://www.ncbi.nlm.nih.gov/pubmed/35986485
http://dx.doi.org/10.1111/ejn.15799
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