A new study by scientists at the San Diego school of
medicine on chronic stress has shown that this condition causes the production
and accumulation of tau proteins in mice brain cells.
The tau protein aggregates observed during the study
conducted on brain cells of mice were similar to the tau proteins that are also
found in Alzheimer's disease in humans.
The results have been published
in the online edition of the Proceedings of the National Academy of Sciences.
Stress is a natural response to difficult situations and in the recent years it has also been linked to psychiatric conditions such as anxiety and depression
. On an upbeat note, not all kinds of stress are harmful. 'Acute stress'
, which is event-free and may even prove to be beneficial, is believed to help improve brain plasticity and develop learning.
However the word
'stress' frequently indicates chronic stress, an affected state of mind that
has now integrated in our daily life. Work place troubles, relationship problems,
financial, health or other emotional challenges contribute to chronic stress.
Chronic stress is 'harmful' as it brings about pathological
changes in the body and is known to have severe health implications. The findings from the present
study confirm those made by earlier clinical findings, which suggest that
individuals prone to stress are more likely to develop sporadic Alzheimer's
which, incidentally, accounts for more than 90% of people
When people begin to age their neurons become less
capable of handling the effects of stress. During stressful situations the
hypothalamus of the brain releases the Corticotropin Releasing Hormone (CRH).
The role of the CRH is to stimulate the pituitary gland to release the adrenocorticotropic
which would act on the adrenal glands to release the stress
The pathology of the AD reveals the involvement of two
different proteins, beta-amyloid plaques
and neurofibrillary tangles
. The NFTs comprise of aggregates of a protein called Tau
role of tau protein is to maintain cellular structure and in the building of
In a person with Alzheimer, the end of the tau protein
gets phosphorylated, as a result of which they form aggregates. When the aggregates
amplify they form neurofibrillary tangles that correlate with a person's
cognitive decline, a symptom of Alzheimer's disease. Research on tau proteins
could throw light on the symptoms and progress of AD, which, in turn, would
help in the management of the condition.
During experiments conducted on mouse models
repeated episodes of human-like stress resulted in the phosphorylation and
altered the solubility of neuronal tau proteins. This process is most
evident in the hippocampus, which is the seat of memory and, also the area that
is first and hardest hit during the unfolding of AD pathology.
In the above-said experiments, two corticotrophin -
releasing factor receptors were particularly impacted by stress. Antagonists
against these receptors reduced stress- effects. Drugs are being tried that
modulate the functioning of these receptors.
The critical research however has raised many doubts
First of all, there is no clear-cut evidence to suggest that NFTs cause AD.
Secondly, no cognitive decline was noticed in mice despite the increase in
phosphorylated tau. Thirdly, the possibility that the mice might have got used
to the repeated stress cannot be ruled out and therefore, using a different
kind of stress after a certain period might have been more effective.
Despite the loopholes, this interesting work carried out
by Rissman et al has immense potential but needs added evidence for larger and
Robert A. Rissmann, Michael A. Staup, Allyson Roe Lee, Nicholas J.
Justice, Kenner C. Rice, Wylie Vale, and Paul E. Sawchenko (2012):"
Corticotropin-releasing factor receptor-dependent effects of repeated stress on
tau phosphorylation, solubility, and aggregation": PNAS, 2012.