Hippocampal Neurogenesis in Mood Disorders

The hippocampus, a key structure for learning, memory and emotion regulation, exhibits lifelong production of new neurons in its dentate gyrus. Adult hippocampal neurogenesis has emerged as a critical factor in the onset and recovery from mood disorders such as major depressive disorder and bipolar disorder. Reduced proliferation and impaired survival of neural stem cells in the dentate gyrus have been linked to depressive-like phenotypes in both animal models and human post-mortem analyses. Conversely, interventions that enhance neurogenesis—ranging from pharmacological agents to behavioural therapies—often coincide with improvements in mood and cognition. Stressful experiences, dysregulated glucocorticoid signalling and inflammatory processes can all suppress neurogenic capacity, thereby exacerbating emotional dysregulation. Understanding the molecular and circuit-level mechanisms that govern hippocampal neurogenesis offers a promising route to novel antidepressant and mood-stabilising strategies. Recent advances have begun to unravel how specific signalling pathways, cellular microenvironments and neuronal activity patterns interact to shape the resilience or vulnerability of this neurogenic niche.

Research from Nature Portfolio

Targeted activation of adult-born neurons in the dentate gyrus using chemogenetic tools has been shown to produce rapid and sustained alleviation of depressive- and anxiety-like behaviours in rodent models. Suppression of excitability in these newborn cells abolishes the behavioural benefits of conventional antidepressants, demonstrating a direct causal link between neuronal activity and affective state. In a complementary line of work, a single severe restraint stress episode was found to induce long-term depressive-like phenotypes accompanied by reduced hippocampal neurogenesis and altered gene expression in the prefrontal cortex and hippocampus. Remarkably, chronic administration of a selective serotonin reuptake inhibitor could reverse both the behavioural deficits and the loss of newborn cells, highlighting adult neurogenesis as a mechanistic substrate for treatment efficacy.

Hippocampal Neurogenesis in Mood Disorders publication trend

The graph below shows the total number of articles in hippocampal neurogenesis in mood disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Adult hippocampal neurogenesis: The process by which new neurons are generated, mature and integrate into existing circuits in the adult dentate gyrus.

Dentate gyrus: A subregion of the hippocampus where neural stem cells reside and give rise to adult-born granule neurons.

Neural stem cell: A multipotent cell within the hippocampus capable of self-renewal and differentiation into neurons, astrocytes or oligodendrocytes.

Platelet-derived growth factor-BB (PDGF-BB): A signalling molecule that stimulates proliferation and maturation of neural stem and progenitor cells.

Heat shock protein A12A (HSPA12A): A molecular chaperone implicated in regulating glycolytic metabolism and supporting neurogenesis under stress conditions.

References

1. Activating newborn neurons suppresses depression and anxiety-like behaviors. Nature Communications (2019).
2. 24-hour-restraint stress induces long-term depressive-like phenotypes in mice. Scientific Reports (2016).
3. PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus. Advanced Science (2023).
4. HSPA12A controls cerebral lactate homeostasis to maintain hippocampal neurogenesis and mood stabilization. Translational Psychiatry (2023).
5. Necessity of Hippocampal Neurogenesis for the Therapeutic Action of Antidepressants in Adult Nonhuman Primates. PLOS ONE (2011).
6. Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders. Frontiers in Physiology (2015).