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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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.662173/full |
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| author | Attila Gáspár Barbara Hutka Aliz Judit Ernyey Brigitta Tekla Tajti Bence Tamás Varga Zoltán Sándor Zádori István Gyertyán |
| author_facet | Attila Gáspár Barbara Hutka Aliz Judit Ernyey Brigitta Tekla Tajti Bence Tamás Varga Zoltán Sándor Zádori István Gyertyán |
| author_sort | Attila Gáspár |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T00:44:17Z |
| format | Article |
| id | doaj.art-113e7fa20e28434c8f27cd56a54bec2f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T00:44:17Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-113e7fa20e28434c8f27cd56a54bec2f2023-01-05T19:53:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.662173662173Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans RatsAttila GáspárBarbara HutkaAliz Judit ErnyeyBrigitta Tekla TajtiBence Tamás VargaZoltán Sándor ZádoriIstván GyertyánIntracerebroventricularly 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.662173/fullAlzheimer disease modelSTZ icv.cognitive test batterylearning impairmentβ-amyloidphospho-tau |
| spellingShingle | Attila Gáspár Barbara Hutka Aliz Judit Ernyey Brigitta Tekla Tajti Bence Tamás Varga Zoltán Sándor Zádori István Gyertyán Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats Frontiers in Pharmacology Alzheimer disease model STZ icv. cognitive test battery learning impairment β-amyloid phospho-tau |
| 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 | Alzheimer disease model STZ icv. cognitive test battery learning impairment β-amyloid phospho-tau |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.662173/full |
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