Adult-born neurons from the dorsal, intermediate, and ventral regions of the longitudinal axis of the hippocampus exhibit differential sensitivity to glucocorticoids

Levone, Brunno Rocha; Codagnone, Martín Gabriel; Moloney, Gerard M.; Nolan, Yvonne M.; Cryan, John F.; O’Leary, Olivia F.

doi:10.1038/s41380-020-0848-8

Cited by 23 publications

(17 citation statements)

References 65 publications

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“…Stereological assessment of Ki67+ SGZ cells mice 3 dpi revealed an effect of injury ( Figure 2A ), with ∼45% more Ki67+ SGZ cells in LFPI vs. Sham mice (statistics for this and all subsequent measures provided in Supplementary Tables 1, 2 ). As the DG, and thus the SGZ, varies along its longitudinal axis in regard to afferents, efferents, and function ( Scharfman, 2011 ; Wu et al, 2015 ; Levone et al, 2020 ), Ki67+ cells were also quantified in the anterior vs. posterior SGZ with the division defined as −2.60mm relative to Bregma ( Tanti and Belzung, 2013 ). Similar to the analysis on the entire SGZ ( Figure 2A ), analysis of Ki67+ cell number in the anterior and posterior SGZ 3 dpi revealed an effect of injury, with ∼40% ( Figure 2B ) and ∼50% more Ki67+ cells ( Figure 2C ), respectively, in the ipsilateral neurogenic SGZ of LFPI vs. Sham mice.…”

Section: Resultsmentioning

confidence: 99%

Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus

et al. 2021

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Mild traumatic brain injuries (mTBIs) are prevalent worldwide. mTBIs can impair hippocampal-based functions such as memory and cause network hyperexcitability of the dentate gyrus (DG), a key entry point to hippocampal circuitry. One candidate for mediating mTBI-induced hippocampal cognitive and physiological dysfunction is injury-induced changes in the process of DG neurogenesis. There are conflicting results on how TBI impacts the process of DG neurogenesis; this is not surprising given that both the neurogenesis process and the post-injury period are dynamic, and that the quantification of neurogenesis varies widely in the literature. Even within the minority of TBI studies focusing specifically on mild injuries, there is disagreement about if and how mTBI changes the process of DG neurogenesis. Here we utilized a clinically relevant rodent model of mTBI (lateral fluid percussion injury, LFPI), gold-standard markers and quantification of the neurogenesis process, and three time points post-injury to generate a comprehensive picture of how mTBI affects adult hippocampal DG neurogenesis. Male C57BL/6J mice (6-8 weeks old) received either sham surgery or mTBI via LFPI. Proliferating cells, neuroblasts/immature neurons, and surviving cells were quantified via stereology in DG subregions (subgranular zone [SGZ], outer granule cell layer [oGCL], molecular layer, and hilus) at short-term (3 days post-injury, dpi), intermediate (7 dpi), and long-term (31 dpi) time points. The data show this model of mTBI induces transient, sequential increases in ipsilateral SGZ/GCL proliferating cells, neuroblasts/immature neurons, and surviving cells which is suggestive of mTBI-induced neurogenesis. In contrast to these ipsilateral hemisphere findings, measures in the contralateral hemisphere were not increased in key neurogenic DG subregions after LFPI. Our work in this mTBI model is in line with most literature on other and more severe models of TBI in showing TBI stimulates the process of DG neurogenesis. However, as our DG data in mTBI provide temporal, subregional, and neurogenesis-stage resolution, these data are important to consider in regard to the functional importance of TBI-induction of the neurogenesis process and future work assessing the potential of replacing and/or repairing DG neurons in the brain after TBI.

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Section: Resultsmentioning

confidence: 99%

Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus

et al. 2021

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“…Interestingly, Fitzsimons and colleagues showed that GR knock-down in the DG neurogenic niche increased the number of doublecortin (DCX)+ neuroblasts, accelerated their terminal differentiation, and increased basal excitability, in line with the idea that GCs can impair neurogenesis, by altering the excitation-inhibition balance [ 276 ]. More recently, it has been shown that NPCs isolated from the rat ventral hippocampus are more sensitive to the antineurogenic effects of chronic GC treatment compared to the dorsal and the intermediate hippocampus, thus explaining the enhanced susceptibility of NPCs of this hippocampal region to the stress [ 86 ]. In the context of stress, heterozygosity for GR was shown to make mice prone to develop depressive-like behavior and impaired neurogenesis after stress [ 278 , 279 ].…”

Section: Mechanisms Of Stress Acting On Neurogenesismentioning

confidence: 99%

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

Leschik

Lutz

Gentile

2021

IJMS

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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.

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“…2A) , with ~45% more Ki67+ SGZ cells in LFPI vs. Sham mice (statistics for this and all subsequent measures provided in Tables S1 and S2). As the DG, and thus the SGZ, varies along its longitudinal axis in regard to afferents, efferents, and function (Scharfman, 2011; Wu et al, 2015; Levone et al, 2020), Ki67+ cells were also quantified in the anterior vs. posterior SGZ with the division defined as −2.60mm relative to Bregma (Tanti and Belzung, 2013). Similar to the analysis on the entire SGZ (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mild traumatic brain injury induces transient, sequential increases in proliferation, neuroblasts/immature neurons, and cell survival: a time course study in the male mouse dentate gyrus

Clark

Yun

Acquah

et al. 2020

Preprint

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Mild traumatic brain injuries (mTBIs) are prevalent worldwide. mTBIs can impair hippocampal-based functions such as memory and cause network hyperexcitability of the dentate gyrus (DG), a key entry point to hippocampal circuitry. One candidate for mediating mTBI-induced hippocampal cognitive and physiological dysfunction is injury-induced changes in DG neurogenesis, a process that mediates spatial/contextual memory. There are conflicting results on how TBI impacts DG neurogenesis; this is not surprising given that both the neurogenesis process and the post-injury period are dynamic, and that neurogenesis quantification varies widely in the literature. Even within the minority of TBI studies focusing specifically on mild injuries, there is disagreement about if and how mTBI changes DG neurogenesis. Here we utilized a clinically-relevant rodent model of mTBI (lateral fluid percussion injury, LFPI), gold-standard neurogenesis markers and quantification approaches, and three time points post-injury to generate a comprehensive picture of how mTBI affects adult hippocampal DG neurogenesis. Male C57BL/6J mice (6-8 weeks old) received either sham surgery or mTBI via LFPI. Proliferating cells, neuroblasts/immature neurons, and surviving cells were quantified via stereology in DG subregions (subgranular zone [SGZ], outer granule cell layer [GCL], molecular layer, and hilus) at short-term (3 days post-injury, dpi), intermediate (7 dpi), and long-term (31 dpi) time points. The data suggest this model of mTBI induces transient, sequential increases in ipsilateral SGZ/GCL proliferating cells, immature neurons, and surviving cells which are indicative of mTBI-induced neurogenesis. In contrast to these ipsilateral hemisphere findings, measures in the contralateral hemisphere show no increase in neurogenesis indices in the key neurogenic DG subregions. Our work in this mTBI model is in line with the large fraction of literature that reports increased DG neurogenesis in other and more severe models of TBI. As our DG neurogenesis data in this mTBI model provide temporal, subregional, and neurogenesis-stage resolution, these data are important to consider in regard to the functional importance of TBI-induced neurogenesis and future work assessing the potential of replacing and/or repairing DG neurons in the brain after TBI.

show abstract

Adult-born neurons from the dorsal, intermediate, and ventral regions of the longitudinal axis of the hippocampus exhibit differential sensitivity to glucocorticoids

Cited by 23 publications

References 65 publications

Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus

Mild Traumatic Brain Injury Induces Transient, Sequential Increases in Proliferation, Neuroblasts/Immature Neurons, and Cell Survival: A Time Course Study in the Male Mouse Dentate Gyrus

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

Mild traumatic brain injury induces transient, sequential increases in proliferation, neuroblasts/immature neurons, and cell survival: a time course study in the male mouse dentate gyrus

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