scholarly journals Mathematical modelling of adult hippocampal neurogenesis: effects of altered stem cell dynamics on cell counts and bromodeoxyuridine-labelled cells

2014 ◽  
Vol 11 (94) ◽  
pp. 20140144 ◽  
Author(s):  
Frederik Ziebell ◽  
Ana Martin-Villalba ◽  
Anna Marciniak-Czochra
Keyword(s):  
Granule Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Initial Increase ◽  
Model Parameters ◽  
Multiple Time ◽  
Cell Dynamics ◽  
Asymmetric Cell Divisions ◽  
Neurogenic Niche ◽  
Cell Counts

In the adult hippocampus, neurogenesis—the process of generating mature granule cells from adult neural stem cells—occurs throughout the entire lifetime. In order to investigate the involved regulatory mechanisms, knockout (KO) experiments, which modify the dynamic behaviour of this process, were conducted in the past. Evaluating these KOs is a non-trivial task owing to the complicated nature of the hippocampal neurogenic niche. In this study, we model neurogenesis as a multicompartmental system of ordinary differential equations based on experimental data. To analyse the results of KO experiments, we investigate how changes of cell properties, reflected by model parameters, influence the dynamics of cell counts and of the experimentally observed counts of cells labelled by the cell division marker bromodeoxyuridine (BrdU). We find that changing cell proliferation rates or the fraction of self-renewal, reflecting the balance between symmetric and asymmetric cell divisions, may result in multiple time phases in the response of the system, such as an initial increase in cell counts followed by a decrease. Furthermore, these phases may be qualitatively different in cells at different differentiation stages and even between mitotically labelled cells and all cells existing in the system.

scholarly journals JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche

2016 ◽  
Vol 23 (2) ◽  
pp. 362-374 ◽  
Author(s):  
H Mohammad ◽  
F Marchisella ◽  
S Ortega-Martinez ◽  
P Hollos ◽  
K Eerola ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Autonomous Control ◽  
Adult Hippocampal Neurogenesis ◽  
Neurogenic Niche

scholarly journals Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
María Belén Pardi ◽  
Mora Belén Ogando ◽  
Alejandro F Schinder ◽  
Antonia Marin-Burgin
Keyword(s):  
Granule Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Information Encoding ◽  
High Frequencies ◽  
Wide Range ◽  
Mature Neurons ◽  
Different Populations ◽  
Immature Cells ◽  
Two Populations

Adult hippocampal neurogenesis provides the dentate gyrus with heterogeneous populations of granule cells (GC) originated at different times. The contribution of these cells to information encoding is under current investigation. Here, we show that incoming spike trains activate different populations of GC determined by the stimulation frequency and GC age. Immature GC respond to a wider range of stimulus frequencies, whereas mature GC are less responsive at high frequencies. This difference is dictated by feedforward inhibition, which restricts mature GC activation. Yet, the stronger inhibition of mature GC results in a higher temporal fidelity compared to that of immature GC. Thus, hippocampal inputs activate two populations of neurons with variable frequency filters: immature cells, with wide‐range responses, that are reliable transmitters of the incoming frequency, and mature neurons, with narrow frequency response, that are precise at informing the beginning of the stimulus, but with a sparse activity.

scholarly journals Unique Microglial Transcriptomic Signature within the Hippocampal Neurogenic Niche

2021 ◽  
Author(s):  
Sana Chintamen ◽  
Pallavi Gaur ◽  
Nicole Vo ◽  
Elizabeth Bradshaw ◽  
Vilas Menon ◽  
...  
Keyword(s):  
Gene Signature ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Neurogenic Niche ◽  
Expression Of Genes ◽  
Transcriptomic Signature ◽  
Specialized Population ◽  
Lower Expression

Microglia, the resident immune cells of the brain, are crucial in the development of the nervous system. Recent evidence demonstrates that microglia modulate adult hippocampal neurogenesis by inhibiting cell proliferation of neural precursors and survival both in vitro and in vivo, thus maintaining a balance between cell division and cell death in the neural stem cell pool. There are increasing reports suggesting these microglia found in neurogenic niches differ from their counterparts in non-neurogenic areas. Here, we present evidence that microglia in the hippocampal neurogenic niche are a specialized population that express genes known to regulate neurogenesis. By comprehensively profiling myeloid lineage cells in the hippocampus using single cell RNA-sequencing, we resolve transcriptomic differences in microglia originating from the subgranular zone. These cells have lower expression of genes associated with homeostatic microglia and increased expression of genes associated with phagocytosis. Intriguingly, this small yet distinct population expresses a gene signature with substantial overlap with previously characterized phenotypes, including disease associated microglia (DAM), a particularly unique and compelling microglial state.

scholarly journals Comparison of Adult Hippocampal Neurogenesis and Susceptibility to Treadmill Exercise in Nine Mouse Strains

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jong Whi Kim ◽  
Sung Min Nam ◽  
Dae Young Yoo ◽  
Hyo Young Jung ◽  
Il Yong Kim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Genetic Background ◽  
Granule Cells ◽  
Treadmill Exercise ◽  
Inbred Mouse ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mouse Strains ◽  
Neuroblast Differentiation ◽  
Outbred Mouse

The genetic background of mice has various influences on the efficacy of physical exercise, as well as adult neurogenesis in the hippocampus. In this study, we investigated the basal level of hippocampal neurogenesis, as well as the effects of treadmill exercise on adult hippocampal neurogenesis in 9 mouse strains: 8 very commonly used laboratory inbred mouse strains (C57BL/6, BALB/c, A/J, C3H/HeJ, DBA/1, DBA/2, 129/SvJ, and FVB) and 1 outbred mouse strain (ICR). All 9 strains showed diverse basal levels of cell proliferation, neuroblast differentiation, and integration into granule cells in the sedentary group. C57BL/6 mice showed the highest levels of cell proliferation, neuroblast differentiation, and integration into granule cells at basal levels, and the DBA/2 mice showed the lowest levels. The efficacy of integration into granule cells was maximal in ICR mice. Treadmill exercise increased adult hippocampal neurogenesis in all 9 mouse strains. These results suggest that the genetic background of mice affects hippocampal neurogenesis and C57BL/6 mice are the most useful strain to assess basal levels of cell proliferation and neuroblast differentiation, but not maturation into granule cells. In addition, the DBA/2 strain is not suitable for studying hippocampal neurogenesis.

Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior

2017 ◽  
Vol 29 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Martha Pérez-Domínguez ◽  
Luis B. Tovar-y-Romo ◽  
Angélica Zepeda
Keyword(s):  
Stem Cells ◽  
Physical Exercise ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Neural Stem Cells ◽  
Neurogenic Niche ◽  
Glial Lineage

Abstract The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.

scholarly journals Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0183463 ◽  
Author(s):  
Florus Woitke ◽  
Mihai Ceanga ◽  
Max Rudolph ◽  
Fanny Niv ◽  
Otto W. Witte ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Granule Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans

2021 ◽  
Author(s):  
Xiaoqun Wang ◽  
Wei Wang ◽  
Mengdi Wang ◽  
Meng Yang ◽  
Bo Zeng ◽  
...  
Keyword(s):  
Granule Cells ◽  
Interaction Analysis ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Cellular Heterogeneity ◽  
Molecular Characteristics ◽  
Immature Neuron ◽  
Proinflammatory Responses ◽  
Adult Nscs ◽  
Single Nucleus

Abstract Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans remains extensive debates1-8. Here, to provide a better understanding of AHN of primates, droplet-based single nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. We pinpoint the dynamics of the neurogenic lineage, including adult neural stem cells (NSCs) and immature neurons, and the diversity of astrocytes and microglia. In the neurogenic lineage, the regulatory continuum from adult NSCs to immature and mature granule cells is investigated. We identify ETNPPL as a primate-specific NSC marker and verify STMN1 and STMN2 as immature neuron markers in primates. Importantly, we also illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis implies that astrocytes are more important niche cells that provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and thus are attributed to the decrease and variability of AHN in adult and elderly.

scholarly journals Changes in the functional connectome and behavior after exposure to chronic stress and increasing neurogenesis

2020 ◽  
Author(s):  
Luka Culig ◽  
Patrick E. Steadman ◽  
Justin W. Kenney ◽  
Sandra Legendre ◽  
Frédéric Minier ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Granule Cells ◽  
Brain Networks ◽  
Chronic Mild Stress ◽  
Protective Role ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mild Stress ◽  
Brain Circuitry ◽  
Newborn Neurons

AbstractAddition of new neurons to the dentate gyrus might change the activity of neural circuitry in the areas which the hippocampus projects to. The size of the hippocampus and the number of adult newborn granule cells are decreased by unpredictable chronic mild stress (UCMS). Additionally, one of the notable effects of chronic stress is the induction of ΔFosB, an unusually stable transcription factor which accumulates over time in several brain areas. This accumulation has been observed in many animal models of depression and it could have a protective role against stress, but no studies so far have explored how a specific increase in neurogenesis might regulate the induction and which brain networks might be predominately affected.We attempted to investigate the role of increasing adult hippocampal neurogenesis on stress-related behavior and the functional brain circuitry involved in mice exposed to UCMS. We used iBax mice, in which the pro-apoptotic gene Bax can be selectively ablated in neural stem cells, therefore inducibly enhancing survival of newborn neurons after tamoxifen administration. The animals were exposed to UCMS for 9 weeks and treated with tamoxifen in week 3 after the beginning of UCMS. In week 8, they were submitted to a battery of behavioral tests to assess depressive-like and anxiety-like behavior. In week 9, blood was collected to assess basal corticosterone levels, and the animals were sacrificed and their brain collected for ΔFosB immunohistochemistry. Brain-wide maps of ΔFosB expression were constructed and graph theoretical analyses were used to study the changes in brain networks after stress.UCMS induced negative correlations between the lateral entorhinal cortex and both the hippocampal structures and the nucleus accumbens in the VEH-treated mice, which were not present in other groups. Ranking nodes by degree reveals a strong thalamic-cortical signature in both non-stress (NS) groups. Exposure to UCMS seems to induce activity in thalamic areas and cerebral nuclei, with a different signature in the UCMS TAM group, which seems to completely “disengage” the neocortex and has most of its nodes with the most connections in the thalamic areas.

scholarly journals Chronic stress induces significant gene expression changes in the prefrontal cortex alongside alterations in adult hippocampal neurogenesis

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Ksenia Musaelyan ◽  
Selin Yildizoglu ◽  
James Bozeman ◽  
Andrea Du Preez ◽  
Martin Egeland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Dendritic Tree ◽  
Hippocampal Neurogenesis ◽  
Stress Disorders ◽  
Adult Hippocampal Neurogenesis ◽  
Mild Stress ◽  
Neurogenic Niche

Abstract Adult hippocampal neurogenesis is involved in stress-related disorders such as depression, posttraumatic stress disorders, as well as in the mechanism of antidepressant effects. However, the molecular mechanisms involved in these associations remain to be fully explored. In this study, unpredictable chronic mild stress in mice resulted in a deficit in neuronal dendritic tree development and neuroblast migration in the hippocampal neurogenic niche. To investigate molecular pathways underlying neurogenesis alteration, genome-wide gene expression changes were assessed in the prefrontal cortex, hippocampus and the hypothalamus alongside neurogenesis changes. Cluster analysis showed that the transcriptomic signature of chronic stress is much more prominent in the prefrontal cortex compared to the hippocampus and the hypothalamus. Pathway analyses suggested huntingtin, leptin, myelin regulatory factor, methyl-CpG binding protein and brain-derived neurotrophic factor as the top predicted upstream regulators of transcriptomic changes in the prefrontal cortex. Involvement of the satiety regulating pathways (leptin) was corroborated by behavioural data showing increased food reward motivation in stressed mice. Behavioural and gene expression data also suggested circadian rhythm disruption and activation of circadian clock genes such as Period 2. Interestingly, most of these pathways have been previously shown to be involved in the regulation of adult hippocampal neurogenesis. It is possible that activation of these pathways in the prefrontal cortex by chronic stress indirectly affects neuronal differentiation and migration in the hippocampal neurogenic niche via reciprocal connections between the two brain areas.

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