Stress can be defined as any type of change that causes physical, emotional or psychological strain. However, not all types of stress are harmful or even negative. There are a few different types of stress that we encounter viz. Eu-stress, Acute Stress, Episodic Acute Stress, Chronic Stress. Stress manifests itself in the form of many psychological and physical problems like anxiety, hopelessness, anger, helplessness, egoism, expectation, tension, constipation, irritation, depression, apathy, frustration, loss of memory, loss of mind’s balance and finally suicide. It has also been reported that people suffering from stress are more likely to be psychologically distressed than those who are not.
According to a recent study published in March 26 issue of PNAS by team of researchers at University of California, San Diego School of Medicine, repeated stress triggers the production and accumulation of insoluble tau protein aggregates inside the brain cells of mice which may define a link between stress and an AD-related pathogenic mechanism.
The aggregates are similar to neurofibrillary tangles or NFTs, modified protein structures that are one of the physiological hallmarks of Alzheimer’s disease. The findings may at least partly explain why clinical studies have found a strong link between people prone to stress and development of sporadic Alzheimer’s disease (AD), which accounts for up to 95 percent of all AD cases in humans.
Using rodent models researcheres found that repeated episodes of emotional stress, which has been demonstrated to be comparable to what humans might experience in ordinary life, resulted in the phosphorylation and altered solubility of tau proteins in neurons, these events are critical in the development of NFT pathology in Alzheimer’s disease.
The effect was most notable in the hippocampus, a region of the brain linked to the formation, organization and storage of memories. In AD patients, the hippocampus is typically the first region of the brain affected by tau pathology and the hardest-hit, with substantial cell death and shrinkage.
Not all forms of stress are equally threatening. In earlier research, Rissman and colleagues reported that acute stress — a single, passing episode — does not result in lasting, debilitating long lasting changes in accumulation of phosphorylated tau. Acute stress-induced modifications in the cell are transient and on the whole, probably beneficial.
Researchers added that, “Acute stress may be useful for brain plasticity and helping to facilitate learning. Chronic stress and continuous activation of stress pathways may lead to pathological changes in stress circuitry. As people age, perhaps their neuronal circuits becoming less robust and perhaps less capable of completely rebounding from the effects of stress. Age is the primary, known risk factor for Alzheimer’s disease. It may be that as we age, our neurons just aren’t as plastic as they once were and some succumb.”
The researchers observed that stress cues impacted two key corticotropin-releasing factor receptors, suggesting a target for potential therapies. Authors also discussed the drugs that already exist and are in human trials (for other conditions) that modulate the activity of these receptors. Although we can’t just eliminate stress. We all need to be able to respond at some level to stressful stimuli. The idea is to use an antagonist molecule to reduce the effects of stress upon neurons. The stress system can still respond, but the response in the brain and hippocampus would be toned down so that it doesn’t result in harmful, permanent damage.
In the acknowledgement, authors dedicate this work to long time mentor and colleague, Dr. Wylie Vale, whose years of pioneering work deciphering and describing the stress system were fundamental to this paper. Vale passed away earlier this year at the age of 70
Rissman RA, Staup MA, Lee AR, Justice NJ, Rice KC, Vale W, & Sawchenko PE (2012). Corticotropin-releasing factor receptor-dependent effects of repeated stress on tau phosphorylation, solubility, and aggregation. Proceedings of the National Academy of Sciences of the United States of America PMID: 22451915