Dendritic spine plasticity in depression

Abstract

Depression is a mental disorder that is estimated by the World Health Organization to affect 350 million people worldwide. Depression is a leading cause of disability that severely affects the patient’s work and life. Although the number of individuals with depression is constantly growing, the understanding of the pathogenesis of depression is still insufficient and effective treatments are lacking. Antidepressants are commonly used as treatments for depression, such as selective serotonin reuptake inhibitors, which increase the availability of synaptic monoamine neurotransmitters. The use of these treatments is based on the theory that neurotransmitter imbalances lead to depression. However, the therapeutic effects of these antidepressants emerge only after weeks of chronic administration, even though they increase the availability of synaptic monoamine levels within hours, which suggest that this hypothesis is insufficient. Furthermore, these antidepressants also show a high percentage of treatment resistance. Despite decades of research, the pathogenesis of depression is still not clear. Our limited understanding could be due to the lack of high-resolution longitudinal studies of the pathological changes in the progression of depression in patients. Thus, a better understanding of the pathogenesis of depression and new drug interventions with higher efficacy and faster onset of therapeutic effects are needed to tackle this devastating mental illness. For a better understanding of the pathogenesis of depression and the underlying mechanisms of antidepressants, we used an animal model of depression with in vivo imaging to study the short- and long-term dendritic spine plasticity in the progression of depression by high-resolution two-photon microscopy. We also explored the antidepressant effects of ketamine in regards to its short- and long-term effects on dendritic spine plasticity in the animal depression model.