Environmental Enrichment: An Alternative Therapy of Neurodegenerative Diseases

By Sanket Rege

Environmental enrichment (EE) is the effect of enhanced sensory, motor, and cognitive stimulation on the neural circuitry of the brain. The evidence for this has been established by studies with enriched housing conditions for rodents and its effects on their brains in comparison to those in normal housing conditions. The idea behind the experimental paradigm is that rodents exposed to an enriched environment have enhanced stimulation of their sensory, motor, and cognitive systems and thus have a more refined neural circuitry. The result is a modified progression of cognitive decline associated with aging and neurodegenerative disorders like Alzheimer’s disease (AD). Enrichment studies have been conducted on mouse models of AD to determine its precise cellular and molecular effects on disease pathology. A significant positive effect would mean a potential for new strategies in therapeutic research.

EE typically involves the provision of a much larger cage for rodents, along with more animals per cage to enhance social stimuli. Sensory stimuli can be enriched by the placement of objects of different size, color, texture, smell, etc., while enriched motor stimuli are achieved by access to a running wheel and cognitive stimuli are driven by spatial mapping of placement of objects in the cage. (Nithianantharajah J., & Hannan A. 2006). One of the findings from such studies was an increase in hippocampal neurogenesis and integration of the newly formed neurons into the circuitry (van Praag H, et al. 2000). The hippocampus can be thought of as the directory to our memories; while it does not store memory itself, it is critical for the storage and retrieval of memories from the cortices. This highlights the hippocampus as a vulnerable structure in many neurodegenerative diseases that result in cognitive decline and memory impairment. The possibility of enhancing neurogenesis in such an area of the brain suggests EE has the potential to facilitate protective effects against neurodegenerative disorders and the natural progression of aging in the brain. Studies have also demonstrated that EE helps delay the manifestation of AD-like behavioral symptoms in AD mouse models and protects against AD-like cognitive impairment (Pietropaolo S, et al. 2008, Costa D, et al. 2007). This suggests that neurogenesis resulting from EE allows the hippocampus to better cope with the increasing demands on the brain resulting from neurodegeneration associated with the disease (Kempermann G, et al. 2008).

The primary goal of EE studies is to discern if it would be useful to humans. If it turns out so, then the applications could be far and wide. EE could be utilized to slow the cognitive decline associated with aging, as a protective measure for individuals predisposed to neurodegenerative disorders, as a therapeutic measure to alleviate symptoms of neurodegeneration, or to simply slow the progression of the disease.

It is much more difficult to generate direct evidence for these studies in humans as it requires substantial histological analyses from brain autopsies and there are several confounding factors to consider due to the varied life-styles of individuals, making it nearly impossible to control for all the variables and truly assess the effect of the enrichment variable. In spite of this, researchers have found a positive correlation between the level of education and the complexity of dendritic branches in the Wernicke’s area of the brain that is involved in the production of written and spoken language (Jacobs B, et al. 1993). More recently, studies have revealed that higher education that is considered more cognitively challenging is associated with diminished effects of aging, dementia, and AD (Fritsch T, et al. 2007; Hall CB, et al. 2007; Roe CM, et al. 2008). MRI studies have also shown that there is a significant increase in grey matter volume within the cerebral cortex after the learning of complex tasks such as juggling or reading through a mirror (Draganski B, et al. 2004; Ilg R, et al. 2008). These studies indicate that the EE could be just as effective in humans as it is proving to be in animal studies. For the longest time it was believe that neurogenesis and plasticity was only significantly increased during neurodevelopment. However, the studies on EE with animals and humans prove that it is still possible at later stages of life. There is one study that even hypothesizes the possibility of developing drugs that would mimic the effects of EE (Herring A, et al. 2008). If the mechanism behind effects of enriched stimulation on the brain were deciphered, the possibility of making “enviromimetic drugs” would not be far away, thus allowing EE to be a genuine treatment option for people regardless of the enrichments opportunities available to them. In the meantime, it would seem that continuing with higher levels of education has an incentive beyond that of just acquiring a good job.

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