Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?

Abstract

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.

Analysis of the Selective Antagonist SAFit2 as a Chemical Probe for the FK506-Binding Protein 51

“…75 There is mounting evidence that hippocampal neurogenesis is likely to play a protecting role against stress-related diseases as a mechanism of resilience. 76, 77 Codagnone et al showed that in primary hippocampal cultures derived from C57BL/6 mice, SAFit2 could increase neurite length, neuronal ramification, and complexity; in rat hippocampal neuronal progenitor cells (NPCs) SAFit2 promoted neurogenesis, neurite outgrowth, and morphological maturation. 74 These results are in line with and further corroborate previous findings reported by Gaali et al, where incubation of human neuroblastoma cells (SH-SY5Y) and mouse neuroblastoma cells (N2a) with SAFit1 showed neurotrophic effects.…”

Theanine, a Tea-Leaf-Specific Amino Acid, Alleviates Stress through Modulation of Npas4 Expression in Group-Housed Older Mice

“…Therefore, it has been proposed that theanine modulates the glutamate–glutamine cycle and inhibits the release of excess excitatory neurotransmitter glutamate [ 10 ]. In addition, neurogenesis in the hippocampus is an important target in stress-induced diseases [ 11 ], and theanine has been reported to upregulate the expression of Slc38a1, one of the glutamine transporter isoforms, and promote neuronal differentiation and proliferation [ 12 ].…”

Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress

“…Specifically, adult hippocampal neurogenesis (AHN), which occurs in the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), participates in learning and memory as well as emotional and motivational regulation [4]. This process is deleteriously affected by stress [5] and perturbations in AHN dynamics have been associated with MDD pathophysiology [3,6]. In line with this, human data shows that prolonged exposure to stress results in the reduction of hippocampal volume, dendritic arborization, and AHN [7] whereas resilience is associated with larger DG volumes [8].…”