Depression and Hippocampal Neurogenesis: A Road to Remission?

Abstract

Adult-generated hippocampal neurons are required for mood control and antidepressant efficacy, raising hopes that someday we can harness the power of new neurons to treat mood disorders such as depression. However, conflicting findings from preclinical research – involving stress, depression, and neurogenesis – highlight the complexity of considering neurogenesis as a “road to remission” from depression. To reconcile differences in the literature, we introduce the “neurogenic interactome”, a platform from which to consider the diverse and dynamic factors regulating neurogenesis. We propose consideration of the varying perspectives – system, region, and local regulation of neurogenesis – offered by the interactome and exchange of ideas between the fields of learning/memory and mood disorder research to clarify the role of neurogenesis in the etiology and treatment of depression.

Impaired Thinking in Patients with Breast Cancer and Depression

“…This finding supports the hypothesis that inflammation reduces neuroplasticity by down-regulation of BDNF as the underlying pathophysiology of depression [3]. BDNF emerged as strong positive determinant of short-term memory and Piaget tasks.…”

“…Brain-derived neurotropic factor (BDNF) has been shown to play a key role in neuronal plasticity, especially in brain regions pertinent to cognition and regulation of mood [1][2][3]. Depression is the most common mood disorder in the advanced cancer setting and often associated with an impaired cognitive function [4].…”

Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury

“…Numerous groups have reported suppressed hippocampal neurogenesis in depressed subjects and increased adult-born hippocampal neurons with antidepressive drug actions. 34,[57][58][59][60] Remote hippocampal neurogenesis also is inhibited in some chronic pain models evoked by peripheral nerve injury that is associated with depression. 35,37 Assessments of neurogenesis in the brain after SCI have been controversial.…”

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

“…Stress, the main cause of depression, most severely affects hippocampal formation (McEwen et al, 2012), while hippocampal subgranular zone (SGZ) of the dentate gyrus (DG) is a region where new neurons originate throughout mammalian adulthood. Moreover, stress leads to significant decrease of adult neurogenesis (for review see Warner- Schmidt and Duman, 2006), implicating a role of this decrease in the onset of depression-like symptoms, however, this notion remains controversial (for reviews see Sahay and Hen, 2007;Balu and Lucki, 2009;Eisch and Petrik, 2012).…”