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Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats

Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque...

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Autores principales: Gáspár, Attila, Hutka, Barbara, Ernyey, Aliz Judit, Tajti, Brigitta Tekla, Varga, Bence Tamás, Zádori, Zoltán Sándor, Gyertyán, István
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138205/
https://www.ncbi.nlm.nih.gov/pubmed/34025423
http://dx.doi.org/10.3389/fphar.2021.662173
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author Gáspár, Attila
Hutka, Barbara
Ernyey, Aliz Judit
Tajti, Brigitta Tekla
Varga, Bence Tamás
Zádori, Zoltán Sándor
Gyertyán, István
author_facet Gáspár, Attila
Hutka, Barbara
Ernyey, Aliz Judit
Tajti, Brigitta Tekla
Varga, Bence Tamás
Zádori, Zoltán Sándor
Gyertyán, István
author_sort Gáspár, Attila
collection PubMed
description Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque-like deposits). However, the model has predominantly been used with Wistar rats in the literature. The objective of the current study was to transfer it to Long-Evans rats with the ulterior aim to integrate it in a complex cognitive test battery where we use this strain because of its superior cognitive capabilities. We performed two experiments (EXP1, EXP2) with three months old male animals. At EXP1, rats were treated with 2 × 1.5 mg/kg STZ (based on the literature) or citrate buffer vehicle injected bilaterally into the lateral ventricles on days 1 and 3. At EXP2 animals were treated with 3 × 1.5 mg/kg STZ or citrate buffer vehicle injected in the same way as in EXP1 at days 1, 3, and 5. Learning and memory capabilities of the rats were then tested in the following paradigms: five choice serial reaction time test (daily training, started from week 2 or 8 post surgery in Exp1 or Exp2, respectively, and lasting until the end of the experiment); novel object recognition (NOR) test (at week 8 or 14), passive avoidance (at week 11 or 6) and Morris water-maze (at week 14 or 6). 15 or 14 weeks after the STZ treatment animals were sacrificed and brain phospho-tau/tau protein ratio and β -amyloid level were determined by western blot technique. In EXP1 we could not find any significant difference between the treated and the control groups in any of the assays. In EXP2 we found significant impairment in the NOR test and elevated β-amyloid level in the STZ treated group in addition to slower learning of the five-choice paradigm and a trend for increased phospho-tau/tau ratio. Altogether our findings suggest that the Long-Evans strain may be less sensitive to the STZ treatment than the Wistar rats and higher doses may be needed to trigger pathological changes in these animals. The results also highlight the importance of strain diversity in modelling human diseases.
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spelling pubmed-81382052021-05-22 Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats Gáspár, Attila Hutka, Barbara Ernyey, Aliz Judit Tajti, Brigitta Tekla Varga, Bence Tamás Zádori, Zoltán Sándor Gyertyán, István Front Pharmacol Pharmacology Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque-like deposits). However, the model has predominantly been used with Wistar rats in the literature. The objective of the current study was to transfer it to Long-Evans rats with the ulterior aim to integrate it in a complex cognitive test battery where we use this strain because of its superior cognitive capabilities. We performed two experiments (EXP1, EXP2) with three months old male animals. At EXP1, rats were treated with 2 × 1.5 mg/kg STZ (based on the literature) or citrate buffer vehicle injected bilaterally into the lateral ventricles on days 1 and 3. At EXP2 animals were treated with 3 × 1.5 mg/kg STZ or citrate buffer vehicle injected in the same way as in EXP1 at days 1, 3, and 5. Learning and memory capabilities of the rats were then tested in the following paradigms: five choice serial reaction time test (daily training, started from week 2 or 8 post surgery in Exp1 or Exp2, respectively, and lasting until the end of the experiment); novel object recognition (NOR) test (at week 8 or 14), passive avoidance (at week 11 or 6) and Morris water-maze (at week 14 or 6). 15 or 14 weeks after the STZ treatment animals were sacrificed and brain phospho-tau/tau protein ratio and β -amyloid level were determined by western blot technique. In EXP1 we could not find any significant difference between the treated and the control groups in any of the assays. In EXP2 we found significant impairment in the NOR test and elevated β-amyloid level in the STZ treated group in addition to slower learning of the five-choice paradigm and a trend for increased phospho-tau/tau ratio. Altogether our findings suggest that the Long-Evans strain may be less sensitive to the STZ treatment than the Wistar rats and higher doses may be needed to trigger pathological changes in these animals. The results also highlight the importance of strain diversity in modelling human diseases. Frontiers Media S.A. 2021-05-07 /pmc/articles/PMC8138205/ /pubmed/34025423 http://dx.doi.org/10.3389/fphar.2021.662173 Text en Copyright © 2021 Gáspár, Hutka, Ernyey, Tajti, Varga, Zádori and Gyertyán. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Gáspár, Attila
Hutka, Barbara
Ernyey, Aliz Judit
Tajti, Brigitta Tekla
Varga, Bence Tamás
Zádori, Zoltán Sándor
Gyertyán, István
Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title_full Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title_fullStr Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title_full_unstemmed Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title_short Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
title_sort intracerebroventricularly injected streptozotocin exerts subtle effects on the cognitive performance of long-evans rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138205/
https://www.ncbi.nlm.nih.gov/pubmed/34025423
http://dx.doi.org/10.3389/fphar.2021.662173
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