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Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment

Advances in the early diagnosis and treatment have led to increases in breast cancer survivorship. Survivors report cognitive impairment symptoms such as loss of concentration and learning and memory deficits which significantly reduce the patient’s quality of life. Additional therapies are needed t...

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Autores principales: Ntagwabira, Fabio, Trujillo, Madison, McElroy, Taylor, Brown, Taurean, Simmons, Pilar, Sykes, Delawerence, Allen, Antiño R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880369/
https://www.ncbi.nlm.nih.gov/pubmed/35216124
http://dx.doi.org/10.3390/ijms23042008
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author Ntagwabira, Fabio
Trujillo, Madison
McElroy, Taylor
Brown, Taurean
Simmons, Pilar
Sykes, Delawerence
Allen, Antiño R.
author_facet Ntagwabira, Fabio
Trujillo, Madison
McElroy, Taylor
Brown, Taurean
Simmons, Pilar
Sykes, Delawerence
Allen, Antiño R.
author_sort Ntagwabira, Fabio
collection PubMed
description Advances in the early diagnosis and treatment have led to increases in breast cancer survivorship. Survivors report cognitive impairment symptoms such as loss of concentration and learning and memory deficits which significantly reduce the patient’s quality of life. Additional therapies are needed to prevent these side effects and, the precise mechanisms of action responsible are not fully elucidated. However, increasing evidence points toward the use of neuroprotective compounds with antioxidants and anti-inflammatory properties as tools for conserving learning and memory. Here, we examine the ability of piperlongumine (PL), an alkaloid known to have anti-inflammatory and antioxidant effects, to play a neuroprotective role in 16-week-old female C57BL/6J mice treated with a common breast cancer regimen of doxorubicin, cyclophosphamide, and docetaxel (TAC). During social memory testing, TAC-treated mice exhibited impairment, while TAC/PL co-treated mice did not exhibit measurable social memory deficits. Proteomics analysis showed ERK1/2 signaling is involved in TAC and TAC/PL co-treatment. Reduced Nrf2 mRNA expression was also observed. mRNA levels of Gria2 were increased in TAC treated mice and reduced in TAC/PL co-treated mice. In this study, PL protects against social memory impairment when co-administered with TAC via multifactorial mechanisms involving oxidative stress and synaptic plasticity.
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spelling pubmed-88803692022-02-26 Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment Ntagwabira, Fabio Trujillo, Madison McElroy, Taylor Brown, Taurean Simmons, Pilar Sykes, Delawerence Allen, Antiño R. Int J Mol Sci Article Advances in the early diagnosis and treatment have led to increases in breast cancer survivorship. Survivors report cognitive impairment symptoms such as loss of concentration and learning and memory deficits which significantly reduce the patient’s quality of life. Additional therapies are needed to prevent these side effects and, the precise mechanisms of action responsible are not fully elucidated. However, increasing evidence points toward the use of neuroprotective compounds with antioxidants and anti-inflammatory properties as tools for conserving learning and memory. Here, we examine the ability of piperlongumine (PL), an alkaloid known to have anti-inflammatory and antioxidant effects, to play a neuroprotective role in 16-week-old female C57BL/6J mice treated with a common breast cancer regimen of doxorubicin, cyclophosphamide, and docetaxel (TAC). During social memory testing, TAC-treated mice exhibited impairment, while TAC/PL co-treated mice did not exhibit measurable social memory deficits. Proteomics analysis showed ERK1/2 signaling is involved in TAC and TAC/PL co-treatment. Reduced Nrf2 mRNA expression was also observed. mRNA levels of Gria2 were increased in TAC treated mice and reduced in TAC/PL co-treated mice. In this study, PL protects against social memory impairment when co-administered with TAC via multifactorial mechanisms involving oxidative stress and synaptic plasticity. MDPI 2022-02-11 /pmc/articles/PMC8880369/ /pubmed/35216124 http://dx.doi.org/10.3390/ijms23042008 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ntagwabira, Fabio
Trujillo, Madison
McElroy, Taylor
Brown, Taurean
Simmons, Pilar
Sykes, Delawerence
Allen, Antiño R.
Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title_full Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title_fullStr Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title_full_unstemmed Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title_short Piperlongumine as a Neuro-Protectant in Chemotherapy Induced Cognitive Impairment
title_sort piperlongumine as a neuro-protectant in chemotherapy induced cognitive impairment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880369/
https://www.ncbi.nlm.nih.gov/pubmed/35216124
http://dx.doi.org/10.3390/ijms23042008
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