Stress, stress hormones, and adult neurogenesis.
- Authors
- Schoenfeld, Timothy J; Gould, Elizabeth
- Year
- 2012
- Journal
- Experimental neurology
- PMID
- 21281629
- DOI
- 10.1016/j.expneurol.2011.01.008
- PMCID
- PMC3715962
The dentate gyrus of the hippocampus continues to produce new neurons throughout adulthood. Adult neurogenesis has been linked to hippocampal function, including learning and memory, anxiety regulation and feedback of the stress response. It is thus not surprising that stress, which affects hippocampal function, also alters the production and survival of new neurons. Glucocorticoids, along with other neurochemicals, have been implicated in stress-induced impairment of adult neurogenesis. Paradoxically, increases in corticosterone levels are sometimes associated with enhanced adult neurogenesis in the dentate gyrus. In these circumstances, the factors that buffer against the suppressive influence of elevated glucocorticoids remain unknown; their discovery may provide clues to reversing pathological processes arising from chronic exposure to aversive stress.
Top left: schematic diagram of adult neurogenesis in the dentate gyrus of the hippocampus. Progenitor cells in the subgranular zone (sgz) divide and produce daughter cells. Most of these cells differentiate into excitatory granule cells and integrate into the granule cell layer as they differentiate. At different timepoints during their maturation, new cells express specific biochemical markers, listed below the schematic diagram. Photomicrographs (bottom left) show BrdU labeled cells (arrows, top), and Ki67 labeled cells (arrows, bottom). BrdU is an exogenously applied marker that labels cells in S phase while Ki67 is an endogenous marker of actively cycling. Confocal microscopic images (bottom right) show cells labeled with BrdU (red) and a marker of astroglia (GFAP), immature and mature neurons (Tuj1) and mature neurons (NeuN).
Schematic diagram of the effects of stress and glucocorticoids on principal cell types in the hippocampus. Stress causes release of glucocorticoids which bind to receptors on all principal cell types in the hippocampus. The dentate gyrus contains granule cells which have excitatory connections with pyramidal cells of the CA3 region. CA3 pyramidal cells have excitatory connections to pyramidal cells in the CA1 region, which have excitatory connections to pyramidal cells in the subiculum, the main efferent population in the hippocampus. Pyramidal cells in the subiculum ultimately exert an inhibitory influence over the HPA axis, helping the system to return to baseline after stress. Aversive experiences are known to inhibit adult neurogenesis in the dentate gyrus potentially through elevated levels of glucocorticoids and cytokines. Rewarding experiences, on the other hand, are known to stimulate adult neurogenesis in the dentate gyrus despite elevated levels of glucocorticoids. Factors that protect against elevated glucocorticoids under conditions of rewarding experience remain unknown β some potential candidates include opioids, dopamine, oxytocin and growth factors.
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