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Animal models of chemotherapy-induced cognitive decline in preclinical drug development.

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Title: Animal models of chemotherapy-induced cognitive decline in preclinical drug development.
Authors: John, Jeena (AUTHOR), Kinra, Manas (AUTHOR), Mudgal, Jayesh (AUTHOR), Viswanatha, G. L. (AUTHOR), Nandakumar, K. (AUTHOR)
Source: Psychopharmacology. Nov2021, Vol. 238 Issue 11, p3025-3053. 29p. 1 Diagram, 13 Charts.
Subjects: Cognition disorders, Chemotherapy complications, Long-term memory, Animal models in research, Drug development
Abstract: Rationale: Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person's day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies. Objectives: A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain. Results: Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent. Conclusion: Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Animal models of chemotherapy-induced cognitive decline in preclinical drug development.
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  Data: <searchLink fieldCode="AR" term="%22John%2C+Jeena%22">John, Jeena</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kinra%2C+Manas%22">Kinra, Manas</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mudgal%2C+Jayesh%22">Mudgal, Jayesh</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Viswanatha%2C+G%2E+L%2E%22">Viswanatha, G. L.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Nandakumar%2C+K%2E%22">Nandakumar, K.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Nov2021, Vol. 238 Issue 11, p3025-3053. 29p. 1 Diagram, 13 Charts.
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  Data: <searchLink fieldCode="DE" term="%22Cognition+disorders%22">Cognition disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Chemotherapy+complications%22">Chemotherapy complications</searchLink><br /><searchLink fieldCode="DE" term="%22Long-term+memory%22">Long-term memory</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+models+in+research%22">Animal models in research</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+development%22">Drug development</searchLink>
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  Data: Rationale: Chemotherapy-induced cognitive impairment (CICI), chemobrain, and chemofog are the common terms for mental dysfunction in a cancer patient/survivor under the influence of chemotherapeutics. CICI is manifested as short/long term memory problems and delayed mental processing, which interferes with a person's day-to-day activities. Understanding CICI mechanisms help in developing therapeutic interventions that may alleviate the disease condition. Animal models facilitate critical evaluation to elucidate the underlying mechanisms and form an integral part of verifying different treatment hypotheses and strategies. Objectives: A methodical evaluation of scientific literature is required to understand cognitive changes associated with the use of chemotherapeutic agents in different preclinical studies. This review mainly emphasizes animal models developed with various chemotherapeutic agents individually and in combination, with their proposed mechanisms contributing to the cognitive dysfunction. This review also points toward the analysis of chemobrain in healthy animals to understand the mechanism of interventions in absence of tumor and in tumor-bearing animals to mimic human cancer conditions to screen potential drug candidates against chemobrain. Results: Substantial memory deficit as a result of commonly used chemotherapeutic agents was evidenced in healthy and tumor-bearing animals. Spatial and episodic cognitive impairments, alterations in neurotrophins, oxidative and inflammatory markers, and changes in long-term potentiation were commonly observed changes in different animal models irrespective of the chemotherapeutic agent. Conclusion: Dyscognition exists as one of the serious side effects of cancer chemotherapy. Due to differing mechanisms of chemotherapeutic agents with differing tendencies to alter behavioral and biochemical parameters, chemotherapy may present a significant risk in resulting memory impairments in healthy as well as tumor-bearing animals. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Nov2021
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