Russian researchers have shown that under stress neuroinflammation processes occur in the hippocampus, leading to the degeneration and death of neurons and, finally, in emotional disorders and memory loss. The work is published in the Metabolic Brain Disease journal. The project is supported by a grant from the Russian Science Foundation (RSF).
Hippocampus is the most important structure of the brain, it largely determines the ability of learning and memory formation, as well as emotional states. Besides, the hippocampus undergoes neurodegeneration (up to the death of nerve cells - neurons), in case it is adversely effected by stress.
We are studying the mechanisms of neurodegeneration in the hippocampus. If we know exactly how neurons die, we will be able to develop ways to protect them. Our goal is to understand why the hippocampus among dozens of other parts of the brain is the most sensitive to different forms of stress, - the Head of the Laboratory of Functional Neurochemistry and Deputy Director of the Institute of Higher Nervous Activity and Neurophysiology (IHNAN) of Russian Academy of Sciences, Head of the RSF grant, Dr. of Biological Sciences, Professor, Natalia Gulyaeva says.
The hippocampus, the old (that is, evolutionarily more ancient) cortex, according to many data, is much less resistant to stress than the cerebral cortex (the new cortex).
We assumed, and then confirmed experimentally that this sensitivity of the hippocampus was related to its instability to inflammatory processes in the brain, arising under the influence of stress factors. The neuroinflammation causes damage to the neurons, leading to the subsequent death of neurons and the development of diseases of the brain, - Natalia Gulyaeva says.
Neuroinflammation is the process that occurs in the brain, the chemistry of which is similar to inflammatory processes in the usual understanding, associated with damage to other tissues. Neuroinflammation almost always precedes neurodegeneration (nerve cell death). There are such neurodegenerative diseases as: Alzheimer's disease and Parkinson's disease; neuronal death occurs in case of acute cerebral circulatory disorders (stroke). Recently it has been shown that mental disorders (particularly depression, schizophrenia) are also accompanied by death of neurons.
The researchers assessed the indices of neuroinflammation in the cerebral cortex (the new bark cortex) and in the hippocampus (the old cortex) of laboratory rats exposed to chronic unpredictable stress combined, combining several stress factors (the model of experimental neurosis). Among these factors there were the electric shocks of moderate intensity, prolonged exposure to white noise sound (sound waves of wide range) and restriction of movement. Stressing has been carried out daily for 2 weeks.
It was found that the hippocampus selectively accumulates stress hormones (corticosteroids), triggering neuroinflammation, probably because it has the maximum number of receptors for these hormones. Cortisol is a stress hormone in humans, corticosterone is the one in rats. In response to the accumulation of stress hormones in the hippocampus and cortex, pro-inflammatory (immune) substances (cytokines) are released, they are the molecular indicators of neuroinflammation. One month after termination of the stress it was found that the main level of the pro-inflammatory cytokine (interleukin IL-1β) in the hippocampus remained elevated, whereas in the cerebral cortex of the same amount of cytokine it returned to normal at that time.
Thus, scientists have found out that for a long time after stress exposure was stopped, the process of neuroinflammation in the hippocampus continued for a long time. The consequences of this can be quite sad.
Cessation of chronic stress by itself doesnt save the hippocampus from the damage that has already begun. The experience of chronic stress manifests itself first in emotional and personality disorders (the so-called neurosis), it can cause anxiety and depression; pathological conditions stimulated by chronic stress can develop into high blood pressure, heart attack and stroke. First of all, the hippocampus is affected as a result of chronic stress, it can develop into memory loss (dementia) and emotional disorders, - Natalia Gulyaeva concludes. The results of our study indicate the direction in which we need to develop a therapy for the prevention of degenerative lesions of the hippocampus. This means that the pharmacological technology should take into account that the process of neuroinflammation in the hippocampus has to be prevented.