Pathophysiological Mechanisms of Maternal Separation Stress in Cognitive Dysfunction

Abstract

Maternal separation (MS) animal stress models are commonly used to evaluate the factors affecting cognitive development. These models simulate mother–offspring separation during the lactation period because it is the most critical neurodevelopmental period for exploring the impact of early-life adversities on the risk of various neurological and cognitive disorders that can occur during adulthood. Cognitive dysfunction may result from multiple contradictory mechanisms that have not yet been reviewed. Therefore, in this narrative review, we aim to offer a critical and objective review of studies published in databases, such as PubMed, Google Scholar, and Web of Science, over the last 5 years that have used this stress model to propose a pathophysiological mechanism of MS-induced cognitive dysfunction. Our review reveals that MS induces cognitive dysfunction via the hypothalamic–pituitary–adrenal axis, which may alter neurogenesis and/or apoptosis. Furthermore, MS leads to neuroinflammation, oxidative stress, mitochondrial dysfunction, and accumulation of neuronal aggregates. In conclusion, the MS stress model offers a cost-effective method to evaluate potential therapeutic agents for a variety of neurodegenerative and neuropsychological disorders. Integrating multidisciplinary research into assessments is a comprehensive strategy for the early prevention of these disorders, which is one of the main objectives of the Saudi Arabia 2030 vision for efficient child integration in society.