Scientists from the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences analyzed the behavior of rat pups and proved that pro-inflammatory stress in childhood leads to the development of anxiety-depressive behavior in adulthood. Research on this phenomenon was supported by a grant from the Russian Science Foundation (RSF); its results were published in the journal Behavioral Brain Research .
Pro-inflammatory stress is a stressful effect of a different nature, causing inflammation, in particular, in the brain tissue ( neuroinflammation ). At the same time, the cells of brain microglia , which have the properties of macrophages (cells of the immune system that capture and eliminate foreign or toxic particles), and astrocytes , also glial cells, secrete special chemicals, cytokines, which are mediators of inflammation. In the first stage, inflammation is an adaptive and beneficial process, but sometimes it goes too far. In such cases, excessive secretion of cytokines begins and processes develop that contribute to the degeneration and death of cells, in particular neurons.
“The starting point was quite simple: psychiatrists had long noticed that almost the majority of people with depression experienced some kind of serious stress trauma, such as violence, at an early age. In addition, it is known that problems in infancy or even prenatal age – fetal hypoxia or infection – lead to the development of a variety of diseases, including depression, ”said co-author of the article, Doctor of Biological Sciences, Professor Natalia Gulyaeva, head of the Laboratory of Functional Biochemistry of Nervous systems and deputy director of the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, head of the grant of the Russian Science Foundation.
The goal of the scientists was to find the mechanisms responsible for the development of the disease, so that, by targeting these mechanisms, subsequently stop the process of the disease or even prevent it.
During the experiment, scientists simulated early pro-inflammatory stress by injecting newborn (3-5 day old) rat pups in a small dose of bacterial lipopolysaccharide – a fragment of the bacterial wall that caused inflammatory processes in the body, in particular neuroinflammation . Then we monitored how the behavior of growing animals changes in comparison with control animals that were not exposed to pro-inflammatory stress in adolescence (for rats – one month) and before reaching puberty – three months. In particular, the scientists watched how the rat pups develop symptoms of depression and anxiety, investigated the synaptic plasticity of the brain, which determines the body’s ability to learn and memory.
As a result, scientists have found that rat pups gradually develop symptoms characteristic of psychoemotional disorders. In adolescence, signs of anxiety appeared and depressive-like behavior began to appear , which was already pronounced in adult animals. The synaptic plasticity of the brains of animals was severely impaired by pro – inflammatory stress already in adolescence. Moreover, the level of corticosterone , the stress hormone, has been increased, which means that these animals have a permanent internal stress factor. In a stressful situation, both in humans and in rats, a large amount of this stress hormone is secreted from the adrenal glands (in humans, the hormone cortisol is the analogue of corticosterone ), and this has an adaptive value, mobilizing metabolic processes to overcome stress. However, if the level of corticosterone (or cortisol in a person) is steadily increased, the additional release of the hormone no longer occurs, and this significantly reduces the body’s resistance to stress. So the excess of corticosterone does a double whammy – depletes metabolic sources and weakens the ability to resist stress.
The researchers hope that the results of their work will be introduced into the clinic both for preventive measures when exposed to extreme factors on the child’s body, and for the development of new approaches to treating depression based on the identified new molecular-cell mechanisms.