Erythropoietin – doping for the brain?
To be remembered…Dmitry Chuvelev, STRF.ru
New research in the field of studying the mechanisms of memory shows that erythropoietin improves memory, not only activating hematopoiesis, but also directly affecting the neurons of the brain.
The author of the discovery, Dr. Hannelore Ehrenreich, says: "Patients who received erythropoietin for the treatment of chronic kidney disease showed an improvement in cognitive processes. This effect is considered to be the result of an increase in the rate of hematopoiesis and, as a result, a better supply of fresh blood to the brain. But after the discovery of erythropoietin receptors in the nerve cells of the brain, it became obvious that our first assumption was wrong."
To understand the mechanisms of memory work when using erythropoietin, researchers injected mice with this drug for three weeks (11 doses) – the period is considered sufficient to assess the effects that manifest themselves with prolonged use of the drug. As a result of the experiments, it turned out that mice receiving erythropoietin had a better memory than those animals that received a placebo. Moreover, an improvement in memory and cognitive abilities was observed up to three weeks from the date of the last intake, that is, even when the actual enhanced erythropoiesis was no longer observed. Mice treated with three doses of erythropoietin showed no improvement in memory.
"The mice who were systematically treated with erythropoietin for three weeks clearly improved their memory, and this was noticeable to the same extent as those outstanding athletic achievements made by athletes using erythropoietin to increase endurance," explains Dr. Ehrenreich. Specific memory improvement is associated with the activity of the hippocampus, the part of the brain responsible for learning and perception of new information.
The researchers conducted a series of experiments on hippocampus isolated from mice, during which it was found that erythropoietin directly affected the nerve cells of this cerebral structure. "Erythropoietin had an effect on the short– and long-term synaptic plasticity of the hippocampus, as well as on synaptic transmission," the researcher notes. "The use of erythropoietin increases the efficiency of transmission of nerve impulses in individual hippocampal neurons, which leads to greater short– and long-term synaptic plasticity in the mechanisms of memory."
The discovery will help shed light on the mechanisms of learning and memory. Further research will allow us to better understand the mechanism of interaction with erythropoietin not only of hippocampal nerve cells, but also of the rest of the brain. For example, it may turn out that erythropoietin causes an improvement in motor functions in multiple sclerosis. It is also necessary to pay more attention to the effect of erythropoietin on short- and long-term synaptic plasticity in the treatment of neurodegenerative diseases. The new data may also be applicable in the treatment of Alzheimer's disease.
Specialist's comment
Yulia Mednikova, Laboratory of Neurochemical Mechanisms of Learning and Memory of the Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, Doctor of Biological Sciences:
– Memory is one of the manifestations of higher brain functions. Its mechanisms have not yet been fully disclosed, but I would like to draw attention to the fact that the memory of an object or phenomenon should eventually recreate in nerve cells the structure of impulses, in many ways similar to the one that once arose when meeting with reality. The vast majority of everything we encounter on the path of life is not stored in memory. Only important events and objects are remembered, the structure of responses to which is necessarily accompanied by a late stage of activation of neurons. The total correlate of this late activation is recorded in humans from the surface of the skull in the form of late (400-800 ms) components of evoked potentials. Their absence on a real stimulus will mean that a memorable trace is not formed.
Thus, it is natural to assume that any substance that stimulates memory should be related to the formation of a late and sufficiently long stage of activation of nerve cells. In normal conditions, this function in the nervous system is performed by acetylcholine, a well–known mediator that is released from specialized cholinergic structures of the brain whenever an object causes increased attention and motor response. Experimentally, it was found that the effect of acetylcholine on nerve cells leads to a prolonged increase in the frequency of spontaneous activity, causing exactly the effect that is necessary for memory formation. A similar result can be obtained when activating duplicate brain systems, for example, noradrenergic. But the advantage of cholinergic regulation is the high speed of the process and its exceptional functional selectivity. No other substance can possess these properties, even if it affects the activity of neurons in a similar way to acetylcholine, and receptors for it are found in the nervous system.
The number of pharmacological compounds capable of stimulating memory is very large: these are cholinesterase inhibitors (an enzyme that cleaves acetylcholine), choline, cholinomimetics, dopaminergic transmission activators, piracetam (a derivative of gamma-aminobutyric acid), nerve growth factors, antiopiates. It can also be regulatory peptides: vasopressin, substance P, melanostimulating hormone, analogues of adrenocorticotropic hormone, in particular, the Semax peptide developed by the staff of the Institute of Molecular Genetics of the Russian Academy of Sciences and Moscow State University.
Exogenous administration of these drugs due to the non-selectivity of their action can be effective only with the preservation, at least partially, of the brain's own regulatory mechanisms. Drugs that stimulate the cholinergic function of the brain should be considered the most specific for memory activation. Their use gives the best results if it is accompanied by an increase in the energy supply of the brain, since the high rate of the cholinergic process requires high energy costs.
The stimulating effect of erythropoietin on memory function, discovered by Dr. Hannelore Ehrenreich, seems to be largely attributed to stimulating hematopoiesis and improving the energy supply of the brain. This, in particular, is evidenced by the long-term preservation (up to three weeks) of the memory improvement effect obtained in experiments. It is possible, however, that this drug has a direct effect on nerve cells by a mechanism similar to the action of its own regulators of brain activity. Thus, erythropoietin can be attributed to dual–acting drugs - as well as piracetam, which, along with a stimulating effect on the activity of neurons, improves blood circulation in a number of parts of the brain.
It should not be forgotten, however, that the effect of all the proposed memory stimulants, including erythropoietin, is rather short-lived and does not lead to a more efficient functioning of the brain's own mechanisms, creating only the effect of additional activation of neurons, and even then largely indiscriminate. The best way to preserve all the diversity of adaptive functions of the brain is intensive activity – diverse and, if possible, creative work. An intensively working brain not only requires a constant and significant turnover of acetylcholine and replenishment of cholinergic reserves, but also adequate blood supply to ensure its own adaptive function, including memory function.
The higher parts of the nervous system are most in need of constant activity in order to maintain an optimal mode of functioning. In gerontology, there is even a theory of the "Black Queen", according to which, as Lewis Carroll noted, "you have to run as fast as you can just to stay in the same place" and keep your memory as sharp in old age as it was in youth. Therefore, for patients complaining of memory loss, special exercises are often developed that should intensify brain activity. But it is better to start these exercises at a young age. Learning poems, songs, fairy tales and poems, solving trigonometric equations, searching for patterns and analogies, analyzing natural and social phenomena, painfully resolving emerging contradictions – all this can be called the best and most natural memory stimulators.
Portal "Eternal youth" http://www.vechnayamolodost.ru08.10.2008