Introduction
Depression is one of the most commonly diagnosed mental disorders today. Symptoms typically include loss of interest in life, anhedonia, decreased appetite, and disturbed sleep. The manifestation of depression has a significant negative impact on the quality of life of the patient. Often relapses of depression are observed throughout life, and the pathogenesis of the disease is not fully understood. Studies indicate that one of the physiological causes of depression may be neurotransmitter malfunctions associated with pathologies of the hypothalamic-pituitary system (Bleker et al., 2020).
So, for example, a correlation was observed between the duration of the disease and a decrease in the hippocampus volume in patients with depression (Boldrini et al., 2018). With this disorder, there is a decrease in the size and density of both neurons and glial cells in certain parts of the brain (Fan et al., 2022). Adult neurogenesis is an essential factor in the fight against depressive states. The search for new targets for antidepressants is an urgent task, given the growing need for this type of drug.
There are many different mechanisms of regulation of neurogenesis at different levels. One of these mechanisms is miRNAs, short non-coding RNAs that can regulate the functioning of genes. Reduced microRNA synthesis leads to various neurological diseases, such as Parkinson’s disease (Fan et al., 2022). Regulatory molecules are often secreted by neuroglial cells within specific lipid vesicles – exosomes and microRNAs are no exception. The study of the effect of exosomes carrying miRNAs on neurogenesis in depression is helpful for the development of new antidepressants.
Hypothesis
In this work, the researchers studied the ability of glial cells to transport exosomes with miRNAs into neurons and the effect of this process on neurogenesis in depression. The study was conducted on animal models, namely the model of depression in rats. The study group of rodents was subjected to systematic unpredictable stress to induce a depression-like state (Fan et al., 2022).
The study and control groups of rats were tested using standard methods for studying depression – sucrose preference and forced swim tests. The first test is that the animal is given a choice of plain and sweetened water: the choice in favor of simple water signals depression. During the swim test, the rat is placed in a water container with no way to get out. In depressive states, the time until the cessation of resistance is reduced. These methods make it possible to effectively assess the presence of a depressive-like state in the experimental group of rodents.
Methodology
In this study, the researchers induced depression in experimental animals for five weeks until there were significant differences in sucrose preference and forced swim tests compared with the control group. After that, exosomes and miRNAs were isolated from them and various groups of glial cells. The study was carried out using classical cytological and molecular biological methods. Different cell types were separated using cytofluorometry, and the amount of microRNA was measured using a quantitative polymerase chain reaction (Fan et al., 2022).
The hypothesis of exosome transport into neurons was tested using fluorescent labels. Researchers tested the premise of miR-146a-5p synthesis in specific types of glial cells by disrupting this process at various stages, ranging from silencing the corresponding genes to impaired exosome synthesis and complete elimination of the corresponding glial cells. Related parts of the brain were removed, and the consequences of such interventions for neurogenesis were evaluated. The use of a wide range of methods allow researchers to closely investigate all aspects of the phenomenon under study.
Results
During the work, the researchers showed that miR-146a-5p, transported by specific glial cells in exosomes to neurons, affects neurogenesis in a model of depression in rats. The study’s authors demonstrate that miR-146a-5p affects other miRNAs essential for neurogenesis, thus regulating this process (Fan et al., 2022). The relationship between the decrease in neurogenesis and the manifestation of depression has been shown. Since the studied miRNA inhibits neurogenesis in depression, it is a promising target for antidepressants. The main limitation of the study is the use of an animal model. Further search and testing of potential inhibitors of human miR-146a-5p are significantly complicated.
Conclusion
Studies of purely physiological mechanisms of the development of mental disorders such as depression are very important for psychology. One of the main problems of psychology as a science is the low reproducibility of research results and the lack of theoretical justification. Purely neuroscientific research on how the brain works provides a lot of valuable information about how physiological processes determine the behavior of individuals.
The results of this study are credible, as it is extensive from a methodological point of view. The authors of the work conducted many tests using various genetic, cytological, and molecular biological methods to test their hypothesis. This work focuses on a very narrow subject, such as a specific regulatory molecule, but its results provide significant promise for combating depression. I have encountered the problem of the ineffectiveness of antidepressants, so I consider such fundamental work to be substantial. After reviewing this paper, I realized how difficult it is to develop new drugs to combat mental illness, which makes the problem even more urgent.
References
Bleker, L. S., Van Dammen, L., Leeflang, M. M., Limpens, J., Roseboom, T. J., & De Rooij, S. R. (2020). Hypothalamic-pituitary-adrenal axis and autonomic nervous system reactivity in children prenatally exposed to maternal depression: A systematic review of prospective studies. Neuroscience & Biobehavioral Reviews, 117, 243–252. Web.
Boldrini, M., Fulmore, C., Tartt, A., Simeon, L. R., Pavlova, I., Poposka, V., Rosoklija, G., Stankov, A., Arango, V., Dwork, A. J., Hen, R., & Mann, J. J. (2018). Human hippocampal neurogenesis persists throughout aging. Cell Stem Cell, 22(4), 589-599. Web.
Fan, C., Li, Y., Lan, T., Wang, W., Long, Y., & Yu, S. (2022). Microglia secrete miR-146a-5p-containing exosomes to regulate neurogenesis in depression. Molecular Therapy, 30(3), 1300–1314. Web.