Depression is a common disorder that affects your entire life. In adults, the 12-month prevalence of major depressive disorder is approximately 6%, and the lifetime risk is 15–18%. It is one of the leading causes of disability worldwide. From a clinical perspective, depression is a complex disorder with devastating consequences for patients and their families, causing psychological suffering due to sadness, anxiety, sadness and guilt; decreased cognitive function; and impairment of attention, memory and thinking. Moreover, depression negatively affects decision making and interpretation of facts, leading to poor decisions. Depression is also a risk factor for the development and outcome of many chronic noncommunicable diseases, such as cardiovascular disease and diabetes. Evidence also suggests a small and positive association between depression and overall cancer risk, including liver and lung cancer.
Pharmacological treatment for depression has been available since 1957, with the release of imipramine, a tricyclic antidepressant, and iproniazid, a monoamine oxidase inhibitor. Over more than six decades, many drugs have been marketed to improve the tolerability and safety of antidepressant treatment. However, with some exceptions, the proposed mechanism of action of these drugs was to increase the availability of serotonin, norepinephrine, and dopamine. Although efforts have been made to improve the pharmacological treatment of depression, approximately one third of patients do not respond to conventional antidepressants. This limitation in antidepressant effectiveness may be due to the mechanism of action of available antidepressants. Therefore, it is clinically relevant to develop innovative therapeutic strategies based on the pathophysiological aspects of depression.
Some evidence suggests that chronic inflammatory conditions may be associated with the pathogenesis of depression in recent years. These findings have given researchers the opportunity to develop new anti-inflammatory treatments that could improve the symptoms and progression of depression. We have explored the possible use of stem cell therapy. Our research was based on the anti-inflammatory and neurodegenerative properties of stem cells, which can treat the pathogenic condition that maintains depression.
WHAT CAUSES DEPRESSION?
Over the past 60 years, enormous research efforts have been made to unravel and understand the neurobiological processes underlying depression. The attempt to identify the neurobiological processes and causes of depression began with an understanding of the mechanisms of action of antidepressants. This strategy led to the identification of monoamines and their role in depression. Subsequently, the development of almost all antidepressants was based on these discoveries.
Chronic stress modulates the inflammatory process, which plays a critical role in the neurobiology underlying depression.
Interest in the role of immunological and inflammatory mechanisms in depression is a natural outgrowth of research on the HPA axis, as cortisol may modulate these responses. Moreover, consistent evidence for the role of psychological stress in the development of depression includes changes in immune functions, mainly due to chronic inflammatory conditions.The link between emotional stress, depression and inflammation appears to have evolutionary implications. Some evidence suggests that metabolic, endocrine, and immune responses developed simultaneously. In addition to triggering the fight-or-flight response, stress is characterized by increases in heart rate, blood pressure, cortisol and catecholamine levels. It also activates inflammatory pathways in peripheral blood mononuclear cells. However, when stress exposure occurs continuously and is not resolved, metabolic and physiological responses are triggered that contribute to the formation of chronic inflammatory conditions.
HOW CAN CHRONIC STRESS CAUSED BY INFLAMMATION INCREASE DEPRESSION?
Although acute stress causes a state of immunosuppression, exposure to chronic stress has a pro-inflammatory effect. As a result, the anti-inflammatory state develops into a chronic inflammatory state due to factors caused by exposure to chronic stress, such as catecholamines.
DAMPs are inflammatory signaling proteins released under various levels of stress, including psychological factors…
Once released, it is activated through inflammatory receptor cascades. All events occurring outside the brain must change brain physiology to cause depression. There are three mechanisms by which inflammation in peripheral tissues reaches the brain: through the humoral pathway, proinflammatory cytokines enter the brain; in the neural pathway, the same cytokines bind peripheral afferent nerve fibers, such as the vagus nerve, which stimulates fibers in the brain and transduces central cytokine signals and activated immune cells such as monocytes reach the vasculature and brain parenchyma via transport mechanisms. These different mechanisms work in concert to cause inflammation in the brain.
Consequently, activation of inflammation causes metabolic changes that may contribute to the risk of depression and suicide.
The effect of neuroinflammation affects the function of neurocircuits. Inflammation is associated with decreased responsiveness to rewarding stimuli. Many of these brain changes caused by peripheral inflammation and neuroinflammation have been described in experimental and epidemiological studies associated with chronic exposure to social stress. Child maltreatment is a major risk factor for chronic stress and inflammation in the etiopathogenesis of depression. Early life adversity is considered a risk factor for depression, and the strongest association is with emotional abuse, followed by neglect.A growing body of literature shows that early adverse events can shape immune cell and inflammatory cascades. A meta-analysis by Baumeister et al found that adult survivors of childhood trauma had elevated baseline blood levels of C-reactive protein, IL-6, and TNFα.
CLINICAL USE OF STEM CELLS
Stem cells are defined as adult, unspecialized cells with the ability to self-renew and have high regenerative potential. Adult stem cells can differentiate into multiple cell lineages and activate or inhibit a sequence of molecules involved in anti-inflammatory and anti-apoptotic pathways. Mesenchymal stem cells (MSCs) were first discovered in the bone marrow. However, they can also be isolated from umbilical cord tissue and adipose tissue, among other sources.
Research into the therapeutic use of MSCs has expanded, showing that both allogeneic and autologous transplantation are possible due to the low immunogenicity of these cells and immunomodulatory effects.
THERAPY FOR NEUROINFLAMMATORY DISEASES BASED ON STEM CELLS
Stem cell therapy has become the standard of care for the treatment of both subacute and chronic inflammatory conditions and neurological disorders. Research has shown the potential use of adult stem cell therapy to treat certain neurological diseases such as multiple sclerosis, autoimmune encephalomyelitis, Alzheimer’s disease and other dementia conditions, Parkinson’s disease and epilepsy.Most studies highlight the immunomodulatory nature of adult stem cells, as well as their therapeutic efficacy associated with neurological diseases, in particular by inducing anti-inflammatory conditions.
For example, in epilepsy, seizure activity can induce proinflammatory molecules, thereby influencing the severity and frequency of seizures. cord blood mononuclear cells produced significant improvements in neurological function. Following an attack, brain injury induces a highly regulated cascade of biological events characterized by the release of cytokines, chemokines and protectins in the neuronal microenvironment, which is attenuated by adult stem cell transplantation, reduces inflammatory conditions, and promotes tissue repair through cell-cell interactions and paracrine effects. Moreover, some evidence has shown that adult stem cells stimulate angiogenesis and endothelial repair through paracrine action.
Among the most important mechanisms of action of stem cells is the release of extracellular vesicles carrying soluble factors, microRNAs and organelles. The release of extracellular vesicles was originally thought to be a recycling mechanism by which cells remove unwanted proteins and other molecules. Among the subtypes of extracellular vesicles, significant attention is paid to exosomes https://perfecto-room.com/ekzosomy-biologicheskaya-funkciya-klinicheskij-potencial-i-poleznost-dlya-vosstanovleniya-zdorovya/. Exosomes are small membrane vesicles with a diameter of 40 to 100 nm and various biological molecules, including proteins, lipids and nucleic acids, that can be taken up and act in a biologically active manner on recipient cells.Various studies have described the beneficial effects of MSCs by delivering exosomes instead of cells. Thus, transplantation of MSC cells or exosomes may offer effective and safe non-pharmacological therapy for the treatment of neurological diseases.
Optimistic results obtained from experimental studies involving ECHO and MSCs in the treatment of neurological diseases open up the prospect of developing non-pharmacological cellular methods for the treatment of mental disorders. The study also assessed potential inflammatory modulation in those exposed to stress. Levels of pro- and anti-inflammatory cytokines in various regions of the brain, blood and spleen were also quantified.
The results showed that transplantation of stressed cells: restored spontaneous sucrose consumption in stressed individuals; It had a strong anti-inflammatory effect, increasing levels of the anti-inflammatory cytokine IL-10 in the amygdala, hippocampus, frontal cortex, other areas of the brain, as well as in the spleen and blood; in the same brain and peripheral tissues, a decreasing effect on the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNFa and INF-γ) was also detected; and Decreased levels of oxidized DNA, quantified by 8’2-deoxyguanosine. Thus, the therapeutic use of stem cells has a positive effect on depressive symptoms, and possible mechanisms for this effect include immunomodulation of inflammatory conditions in both the peripheral and central nervous systems.The results of various experimental studies strongly support the potential therapeutic use of stem cells in the treatment of depression.
Cell therapy through transplantation or administration of cellular products such as exosomes to MSCs may have a place in treatment-resistant depression.
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