Plausible Role of Stem Cell Types for Treating and Understanding the Pathophysiology of Depression

Abstract

Major Depressive Disorder (MDD), colloquially known as depression, is a debilitating condition affecting an estimated 3.8% of the population globally, of which 5.0% are adults and 5.7% are above the age of 60. MDD is differentiated from common mood changes and short-lived emotional responses due to subtle alterations in gray and white matter, including the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. It can be detrimental to a person's overall health if it occurs with moderate or severe intensity. It can render a person suffering terribly to perform inadequately in their personal, professional, and social lives. Depression, at its peak, can lead to suicidal thoughts and ideation. Antidepressants manage clinical depression and function by modulating the serotonin, norepinephrine, and dopamine neurotransmitter levels in the brain. Patients with MDD positively respond to antidepressants, but 10-30% do not recuperate or have a partial response accompanied by poor life quality, suicidal ideation, self-injurious behavior, and an increased relapse rate. Recent research shows that mesenchymal stem cells and iPSCs may be responsible for lowering depression by producing more neurons with increased cortical connections. This narrative review discusses the plausible functions of various stem cell types in treating and understanding depression pathophysiology.

Keywords: cytokine hypothesis; depression; mesenchymal stem cells; molecular pathways; monoamine hypothesis; neurogenesis; stem cells.

Figure 1

The monoamine hypothesis of depression. The reduced levels of serotonin, norepinephrine, and dopamine have been observed and are understood as one of the main factors responsible for the generation of depressive symptoms.

Figure 2

Biological factors and clinical manifestations associated with depression. There are multiple biological causes at molecular, genetic, epigenetic, cellular, and systems levels. These causes result in clinical depression and can have a plethora of symptoms that may vary in different individuals.

Figure 3

Shows the role of mesenchymal stem cells (MSCs) and neural stems cells (NSCs) in the management of depression. The reduction in the depressive symptoms in the mice animal model has been observed due to administration of MSCs and NSCs. The MSCs and NSCs have the ability to upregulate the BDNF signaling pathway, which is usually downregulated in patients suffering from depression. The upregulation of the BDNF signaling pathway helps in the stimulation of neurogenesis. Neurogenesis is one of the major biological factors responsible for the development of depression; the increase in neurogenesis helps in relieving the symptoms associated with depression.