According to the results now published, stress induces the production of amyloid beta (Aâ) peptide – the molecule associated with the neural plaques characteristic of the disease – and also makes neurons more vulnerable to Aâ toxicity. Administration of glucocorticoids (GC) - the production of which is the first physiological response to stress – was shown to have the same effect, confirming the role of stress in AD. This last result is particularly important as GC are used to treat Alzheimer’s patients and according to this research instead of helping they might be, instead, contributing to the disease.
Alzheimer’s disease is part of a group of illnesses called amyloidoses, which result from protein failure to fold and work properly (proteins’ shape is directly related to their functionality) leading, instead, to their accumulation as toxic insoluble plaques (or amyloids). In Alzheimer’s the misfolded protein is called Aâ and is found as insoluble plaques in the diseased neurons of patients.
It is known that AD patients can have higher anxiety and GC levels than those found on normal individuals and, in rodent models of AD, it has been found that stress can exacerbate the disease. Furthermore, high stressful conditions leads to cognitive impairments very similar to those found in AD patients. These observations have led researchers C Catania, N Sousa, OFX Almeida and colleagues in Germany, Portugal and the UK to wonder if there could be a causal relationship between stress and AD.
In order to investigate this possible link the researchers tested middle-aged rats in different stressful situations looking into Aâ peptide (and also another molecule called C99) levels in the hippocampus and the prefrontal cortex areas of the rats’ brain.
In fact, the first signs of AD do not correlate with the insoluble plaques of Aâ protein found in the diseased brain, but instead, with the levels of soluble Aâ peptide, while the hippocampus and the prefrontal cortex are the first brain areas affected in AD. Furthermore the Aâ peptide is formed from the breakdown of the amyloid precursor protein APP in a series of consecutive steps that originate a molecule called C99, which, when further degraded/cleaved, creates the Aâ peptide (APP –… – C99 – Aâ). And while Aâ peptide is well known to be neurotoxic, recent reports have indicated that C99 – besides being the precursor of Aâ - has a similar toxicity with both molecules affecting neural function and also cognitive behaviour. This has led Catania, Sousa, Almeida and colleagues to use the brain levels of both Aâ and C99 as a measure of potential neuro-damage and AD development in their experiments. Additionally, the researchers also looked into the consequences of glucocorticoids administration in order to confirm the specific effects of stress in AD, since GC secretion is the first physiological response to stress.
The team of researchers found that stressful situations or injections of GC (which mimic stress) led to an increase of both C99 and, eventually, of Aâ in both the hippocampus and the prefrontal cortex of the rats’ brain. Furthermore, rats with a history of stress were more susceptible to the effects of stress or GC administration, showing bigger increases in C99 levels. It was also observed that administration of soluble Aâ led to a similar increase in C99 in the rats’ brain, supporting results by others that have shown that Aâ can induce its own production, but also suggesting that Aâ, stress and GC induced the same biochemical responses.
Next, Catania and colleagues looked at the animals’ behaviour - as behavioural changes are the hallmark of AD - more specifically, at their learning and memory abilities, as these are the two first cognitive functions affected in the disease. They also looked into the rats’ anxiety levels since AD patients are known to be abnormally anxious.For the analysis of spatial memory abilities, stressed and non-stressed rats were tested in a maze over 4 days while their emotional state was accessed by looking into anxiety levels, locomotion patterns and exploratory behaviour.
Their first conclusion was that, like AD patients, rats put into stressful situations or receiving GC were much more anxious than controls. It was also shown that these rats showed had less exploratory interest than control animals. Spatial reference memory – which is involved in learning with repeated experiences, such as those experienced in the maze – was similarly impaired by stress or administration of GC or Aâ. This last result again supports the conclusion that the GC and Aâ act on DA through the same biochemical mechanism. When stress and GC were applied together, spatial reference memory impairment increased revealing a cumulative effect of the various factors.
In conclusion, Catania, Sousa, Almeida and colleagues show that stress can contribute to Alzheimer’s disease in two ways: by inducing the production of known neurotoxic molecules - C99 and Aâ that affect neural function and cognitive behaviour, but also – in the case of existing a previous history of stress – by making animals more susceptible to the C99-inducing effects of GC and Aâ.These results – if further confirmed – have important implications for the understanding of the mechanisms behind Alzheimer’s disease and its predisposing factors and, consequently, also for possible therapeutic approaches.
Catania, Sousa, Almeida and colleagues’ research elucidates the mechanism behind stress and GC direct effect on the brain, and can also be important to understand how stress-mediated diseases, such as depression, affect brain function. The research also alert to the need of investigating further the use of GC in AD therapy and calls for the importance of, when treating AD patients, access previous history of stress or GC therapy.
Piece researched and written by Catarina Amorim – Catarina.Amorim at linacre.ox.ac.uk
Catarina Amorim | alfa
Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine
New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
26.06.2017 | Life Sciences
26.06.2017 | Physics and Astronomy
26.06.2017 | Information Technology