About this Research Topic
Neurotrophins (nerve growth factors (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5)) are a family of secreted growth factors that regulate survival, growth, differentiation, and maintenance of neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). The binding of neurotrophins to their cognate receptors activates different intracellular signaling pathways, which mediate both unique and overlapping functions of neurotrophins in the CNS and PNS.
Depression and addiction are debilitating mental disorders with high rates of relapse and often comorbid with other neuropsychiatric disorders. Stress is a major risk factor in the development of depression and addiction. Previous studies have demonstrated that chronic stress increases vulnerability to depression and addiction, and these disorders in turn lead to altered physiological and molecular responses to stress. Indeed, similar adaptations at molecular or cellular levels have been identified in animal models that produce the core symptoms of depression and addiction.
The role of neurotrophins, in particular BDNF, in mediating stress resilience/susceptibility and depression/addiction has been extensively studied. Advanced technologies such as chemogenetics and optogenetics further allow us to delineate the pathophysiological underpinnings of these disorders at an unprecedented depth. The recent finding that both conventional and rapid-acting antidepressant drugs exert their behavioral effects by directly binding to BDNF receptor TrkB revolutionized our understanding of the molecular mechanisms underlying the antidepressant actions of these agents. However, there are still gaps in our knowledge on the roles of neurotrophins and their receptors in these disorders that need to be filled. For example, the cell type- and circuit-specific contributions of neurotrophins and their receptors to the pathophysiology and treatments of depression and addiction remain a frontier that awaits to be explored. In addition, the role of autophagy, an evolutionarily conserved intracellular process that is regulated by BDNF signaling, in mediating the pathogenesis of depression and addiction is not well understood. Finally, while females and adolescents are at increased risk for developing depression and addiction, few studies have explored the sex differences in neurotrophin signaling pathways at different developmental stages under these pathological conditions.
This Research Topic aims to advance our knowledge on the roles of neurotrophins and their receptors in the pathophysiology and treatments of depression and addiction. We welcome original articles and reviews addressing the themes including, but not limited to:
1. The cell type- and circuit-specific functions of neurotrophins and their receptors in mediating pathophysiology and treatments of depression and/or addiction.
2. The role of neurotrophin signaling-regulated autophagy in depression and/or addiction.
3. The implications of neurotrophins and their receptors in sex differences in stress susceptibility.
4. The interplay between neurotrophins, their receptors, and antidepressant drugs.
5. The interaction between neurotrophins, their receptors, and endogenous opioid system.
6. The role of neurotrophin signaling in depression and/or addiction in different developmental stages.
7. The functions of gene products that are regulated by neurotrophins (e.g. VGF, VEGF, etc.) in depression and/or addiction.
Keywords: Neurotrophins, Neurotrophin Receptors, Depression, Addiction, Pharmacology
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