Why Do We Need to Use Animal Models to Study Cognition and Aging?

Abstract

The article in Neuropsychopharmacology by Solas et al (2010) describes the effects of early stress caused by maternal separation upon cognitive function in adult and aged (18-month-old) rats. The authors argue that the findings may represent proof-of-concept for the use of glucocorticoid or insulin-related drugs in Alzheimer's disease (AD). They used a battery of well-established behavioral tasks, including locomotor behavior, forced swim task (depression test), object recognition task, and Morris water maze in rats. The investigators suggested that neonatal stress may increase age-related cognitive decline and therefore, they argued, it is possible that neonatal exposure to glucocorticoids may have long-term consequences for the rate and degree of cognitive impairment occurring with aging. This would then suggest that drugs that counteract stress hormones may be implicated in the prevention or treatment of severe age-related cognitive disorders such as AD.Cognitive learning in humans is defined as the process of learning by using reason, intuition, and perception. The disadvantage of studying the effects of a specific factor in humans is that cognitive performance in humans is influenced by many factors such as culture, upbringing, education, diet habits, amount of exercise and other activities, as well as motivation and ambition. 'The dynamic polygon hypothesis' for human aging has recently been formulated to describe this cluster of genetic and environmental factors responsible for varying degrees of age-related dementia (see, eg, Fotuhi et al, 2009). The authors proposed that a balance of positive and negative factors can affect the brain throughout the lifespan to determine cognitive performance late in life. This is in line with the findings of Solas et al, and suggests that parallel lines can be drawn between behavioral outcome in rodent and human models for aging, as similar stressors appear to have long-term effects in both species.Fotuhi et al (2009) suggested that a multitude of internal (genetic) and external (environmental) factors increase or decrease the cerebral blood flow, pro-and anti-inflammatory cytokines, insulin-signaling components, growth factors, cortisol, etc., leading to a congruence of physiological processes in the brain making up human learning and memory parameters. As most of the external factors can be controlled in animal models, we often use rodent models for examining the cognitive effects of certain drugs or specific external factors under controlled conditions. In rodents, it is possible to remove one factor at a time to explore how it influences the structural or functional components of the limbic system.The investigators found that neonatal stress gave rise to long-lasting effects on amyloid precursor protein (APP) processing, favoring the amyloidogenic (damaging) type of splicing. To fully explore the role of amyloid in AD, genetic manipulations have been undertaken in mice. Work from other investigators using these transgenic mutated APP models showed that restraint str...

How does caffeine influence memory? Drug, experimental, and demographic factors

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