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Development (Cambridge, England) Feb 2019In the adult rodent brain, neural stem cells (NSCs) persist in the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ), which are specialized niches... (Review)
Review
In the adult rodent brain, neural stem cells (NSCs) persist in the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ), which are specialized niches in which young neurons for the olfactory bulb (OB) and hippocampus, respectively, are generated. Recent studies have significantly modified earlier views on the mechanisms of NSC self-renewal and neurogenesis in the adult brain. Here, we discuss the molecular control, heterogeneity, regional specification and cell division modes of V-SVZ NSCs, and draw comparisons with NSCs in the SGZ. We highlight how V-SVZ NSCs are regulated by local signals from their immediate neighbors, as well as by neurotransmitters and factors that are secreted by distant neurons, the choroid plexus and vasculature. We also review recent advances in single cell RNA analyses that reveal the complexity of adult neurogenesis. These findings set the stage for a better understanding of adult neurogenesis, a process that one day may inspire new approaches to brain repair.
Topics: Adult Stem Cells; Animals; Cell Communication; Cell Differentiation; Cell Lineage; Embryonic Stem Cells; Hippocampus; Humans; Interneurons; Lateral Ventricles; Mice; Neural Stem Cells; Neurogenesis; Neurons; Olfactory Bulb; Sequence Analysis, RNA; Signal Transduction; Single-Cell Analysis; Transcriptome
PubMed: 30777863
DOI: 10.1242/dev.156059 -
Cells Nov 2021Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3's role in the central nervous system has been... (Review)
Review
Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3's role in the central nervous system has been less studied than in the immune system. However, recent studies show it exacerbates Alzheimer's disease and is upregulated in a large variety of brain injuries, while loss of Gal-3 function can diminish symptoms of neurodegenerative diseases such as Alzheimer's. Several novel molecular pathways for Gal-3 were recently uncovered. It is a natural ligand for TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like receptor 4), and IR (insulin receptor). Gal-3 regulates a number of pathways including stimulation of bone morphogenetic protein (BMP) signaling and modulating Wnt signalling in a context-dependent manner. Gal-3 typically acts in pathology but is now known to affect subventricular zone (SVZ) neurogenesis and gliogenesis in the healthy brain. Despite its myriad interactors, Gal-3 has surprisingly specific and important functions in regulating SVZ neurogenesis in disease. Gal-1, a similar lectin often co-expressed with Gal-3, also has profound effects on brain pathology and adult neurogenesis. Remarkably, Gal-3's carbohydrate recognition domain bears structural similarity to the SARS-CoV-2 virus spike protein necessary for cell entry. Gal-3 can be targeted pharmacologically and is a valid target for several diseases involving brain inflammation. The wealth of molecular pathways now known further suggest its modulation could be therapeutically useful.
Topics: Animals; Brain; COVID-19; Cell Movement; Galectin 3; Humans; Inflammation; Lateral Ventricles; Nervous System Diseases; Neural Stem Cells; Neurogenesis; Signal Transduction
PubMed: 34831271
DOI: 10.3390/cells10113047 -
Neuro-oncology Sep 2022Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain...
BACKGROUND
Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain unresolved.
METHODS
Here, we used single-cell RNA sequencing to analyze new and recurrent glioblastoma and the nearby subventricular zone (SVZ).
RESULTS
We found 4 glioblastoma neural lineages are present in new and recurrent glioblastoma with an enrichment of the cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. Cancer lineages were hierarchically organized around cycling oligodendrocytic and astrocytic progenitors that are transcriptomically similar but distinct to SVZ neural stem cells (NSCs). Furthermore, NSCs from the SVZ of patients with glioblastoma harbored glioblastoma chromosomal anomalies. Lastly, mesenchymal cancer cells and TME reactive astrocytes shared similar gene signatures which were induced by radiotherapy in a myeloid-dependent fashion in vivo.
CONCLUSION
These data reveal the dynamic, immune-dependent nature of glioblastoma's response to treatments and identify distant NSCs as likely cells of origin.
Topics: Brain Neoplasms; Glioblastoma; Humans; Lateral Ventricles; Neural Stem Cells; Single-Cell Analysis; Tumor Microenvironment
PubMed: 35416251
DOI: 10.1093/neuonc/noac085 -
Cells Jul 2023Neural progenitor cells (NPCs) are multipotent neural stem cells (NSCs) capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. In... (Review)
Review
Neural progenitor cells (NPCs) are multipotent neural stem cells (NSCs) capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. In the postnatal/adult brain, NPCs are primarily located in the subventricular zone (SVZ) of the lateral ventricles (LVs) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). There is evidence that NPCs are also present in the postnatal/adult hypothalamus, a highly conserved brain region involved in the regulation of core homeostatic processes, such as feeding, metabolism, reproduction, neuroendocrine integration and autonomic output. In the rodent postnatal/adult hypothalamus, NPCs mainly comprise different subtypes of tanycytes lining the wall of the 3 ventricle. In the postnatal/adult human hypothalamus, the neurogenic niche is constituted by tanycytes at the floor of the 3 ventricle, ependymal cells and ribbon cells (showing a gap-and-ribbon organization similar to that in the SVZ), as well as suprachiasmatic cells. We speculate that in the postnatal/adult human hypothalamus, neurogenesis occurs in a highly complex, exquisitely sophisticated neurogenic niche consisting of at least four subniches; this structure has a key role in the regulation of extrahypothalamic neurogenesis, and hypothalamic and extrahypothalamic neural circuits, partly through the release of neurotransmitters, neuropeptides, extracellular vesicles (EVs) and non-coding RNAs (ncRNAs).
Topics: Adult; Humans; Neural Stem Cells; Neurons; Hypothalamus; Brain; Lateral Ventricles
PubMed: 37508487
DOI: 10.3390/cells12141822 -
JCI Insight Jun 2023Radiographic contact of glioblastoma (GBM) tumors with the lateral ventricle and adjacent stem cell niche correlates with poor patient prognosis, but the cellular basis...
Radiographic contact of glioblastoma (GBM) tumors with the lateral ventricle and adjacent stem cell niche correlates with poor patient prognosis, but the cellular basis of this difference is unclear. Here, we reveal and functionally characterize distinct immune microenvironments that predominate in subtypes of GBM distinguished by proximity to the lateral ventricle. Mass cytometry analysis of isocitrate dehydrogenase wild-type human tumors identified elevated T cell checkpoint receptor expression and greater abundance of a specific CD32+CD44+HLA-DRhi macrophage population in ventricle-contacting GBM. Multiple computational analysis approaches, phospho-specific cytometry, and focal resection of GBMs validated and extended these findings. Phospho-flow quantified cytokine-induced immune cell signaling in ventricle-contacting GBM, revealing differential signaling between GBM subtypes. Subregion analysis within a given tumor supported initial findings and revealed intratumor compartmentalization of T cell memory and exhaustion phenotypes within GBM subtypes. Collectively, these results characterize immunotherapeutically targetable features of macrophages and suppressed lymphocytes in GBMs defined by MRI-detectable lateral ventricle contact.
Topics: Humans; Lateral Ventricles; Glioblastoma; Brain Neoplasms; Lymphocytes; Macrophages; Tumor Microenvironment
PubMed: 37192001
DOI: 10.1172/jci.insight.160652 -
The Cochrane Database of Systematic... Mar 2020Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year.
OBJECTIVES
To assess the diagnostic accuracy of structural magnetic resonance imaging (MRI) for the early diagnosis of dementia due to Alzheimer's disease in people with MCI versus the clinical follow-up diagnosis of Alzheimer's disease dementia as a reference standard (delayed verification). To investigate sources of heterogeneity in accuracy, such as the use of qualitative visual assessment or quantitative volumetric measurements, including manual or automatic (MRI) techniques, or the length of follow-up, and age of participants. MRI was evaluated as an add-on test in addition to clinical diagnosis of MCI to improve early diagnosis of dementia due to Alzheimer's disease in people with MCI.
SEARCH METHODS
On 29 January 2019 we searched Cochrane Dementia and Cognitive Improvement's Specialised Register and the databases, MEDLINE, Embase, BIOSIS Previews, Science Citation Index, PsycINFO, and LILACS. We also searched the reference lists of all eligible studies identified by the electronic searches.
SELECTION CRITERIA
We considered cohort studies of any size that included prospectively recruited people of any age with a diagnosis of MCI. We included studies that compared the diagnostic test accuracy of baseline structural MRI versus the clinical follow-up diagnosis of Alzheimer's disease dementia (delayed verification). We did not exclude studies on the basis of length of follow-up. We included studies that used either qualitative visual assessment or quantitative volumetric measurements of MRI to detect atrophy in the whole brain or in specific brain regions, such as the hippocampus, medial temporal lobe, lateral ventricles, entorhinal cortex, medial temporal gyrus, lateral temporal lobe, amygdala, and cortical grey matter.
DATA COLLECTION AND ANALYSIS
Four teams of two review authors each independently reviewed titles and abstracts of articles identified by the search strategy. Two teams of two review authors each independently assessed the selected full-text articles for eligibility, extracted data and solved disagreements by consensus. Two review authors independently assessed the quality of studies using the QUADAS-2 tool. We used the hierarchical summary receiver operating characteristic (HSROC) model to fit summary ROC curves and to obtain overall measures of relative accuracy in subgroup analyses. We also used these models to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available.
MAIN RESULTS
We included 33 studies, published from 1999 to 2019, with 3935 participants of whom 1341 (34%) progressed to Alzheimer's disease dementia and 2594 (66%) did not. Of the participants who did not progress to Alzheimer's disease dementia, 2561 (99%) remained stable MCI and 33 (1%) progressed to other types of dementia. The median proportion of women was 53% and the mean age of participants ranged from 63 to 87 years (median 73 years). The mean length of clinical follow-up ranged from 1 to 7.6 years (median 2 years). Most studies were of poor methodological quality due to risk of bias for participant selection or the index test, or both. Most of the included studies reported data on the volume of the total hippocampus (pooled mean sensitivity 0.73 (95% confidence interval (CI) 0.64 to 0.80); pooled mean specificity 0.71 (95% CI 0.65 to 0.77); 22 studies, 2209 participants). This evidence was of low certainty due to risk of bias and inconsistency. Seven studies reported data on the atrophy of the medial temporal lobe (mean sensitivity 0.64 (95% CI 0.53 to 0.73); mean specificity 0.65 (95% CI 0.51 to 0.76); 1077 participants) and five studies on the volume of the lateral ventricles (mean sensitivity 0.57 (95% CI 0.49 to 0.65); mean specificity 0.64 (95% CI 0.59 to 0.70); 1077 participants). This evidence was of moderate certainty due to risk of bias. Four studies with 529 participants analysed the volume of the total entorhinal cortex and four studies with 424 participants analysed the volume of the whole brain. We did not estimate pooled sensitivity and specificity for the volume of these two regions because available data were sparse and heterogeneous. We could not statistically evaluate the volumes of the lateral temporal lobe, amygdala, medial temporal gyrus, or cortical grey matter assessed in small individual studies. We found no evidence of a difference between studies in the accuracy of the total hippocampal volume with regards to duration of follow-up or age of participants, but the manual MRI technique was superior to automatic techniques in mixed (mostly indirect) comparisons. We did not assess the relative accuracy of the volumes of different brain regions measured by MRI because only indirect comparisons were available, studies were heterogeneous, and the overall accuracy of all regions was moderate.
AUTHORS' CONCLUSIONS
The volume of hippocampus or medial temporal lobe, the most studied brain regions, showed low sensitivity and specificity and did not qualify structural MRI as a stand-alone add-on test for an early diagnosis of dementia due to Alzheimer's disease in people with MCI. This is consistent with international guidelines, which recommend imaging to exclude non-degenerative or surgical causes of cognitive impairment and not to diagnose dementia due to Alzheimer's disease. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future research should not focus on a single biomarker, but rather on combinations of biomarkers to improve an early diagnosis of Alzheimer's disease dementia.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Atrophy; Brain; Cognitive Dysfunction; Disease Progression; Entorhinal Cortex; Hippocampus; Humans; Lateral Ventricles; Magnetic Resonance Imaging; Middle Aged; Neuroimaging; Organ Size; Prospective Studies; Sensitivity and Specificity; Temporal Lobe
PubMed: 32119112
DOI: 10.1002/14651858.CD009628.pub2 -
Nature Communications Nov 2021Basal progenitors (BPs), including intermediate progenitors and basal radial glia, are generated from apical radial glia and are enriched in gyrencephalic species like...
Basal progenitors (BPs), including intermediate progenitors and basal radial glia, are generated from apical radial glia and are enriched in gyrencephalic species like humans, contributing to neuronal expansion. Shortly after generation, BPs delaminate towards the subventricular zone, where they further proliferate before differentiation. Gene expression alterations involved in BP delamination and function in humans are poorly understood. Here, we study the role of LGALS3BP, so far known as a cancer biomarker, which is a secreted protein enriched in human neural progenitors (NPCs). We show that individuals with LGALS3BP de novo variants exhibit altered local gyrification, sulcal depth, surface area and thickness in their cortex. Additionally, using cerebral organoids, human fetal tissues and mice, we show that LGALS3BP regulates the position of NPCs. Single-cell RNA-sequencing and proteomics reveal that LGALS3BP-mediated mechanisms involve the extracellular matrix in NPCs' anchoring and migration within the human brain. We propose that its temporal expression influences NPCs' delamination, corticogenesis and gyrification extrinsically.
Topics: Animals; Antigens, Neoplasm; Biomarkers, Tumor; Cell Differentiation; Cerebral Cortex; Extracellular Vesicles; Female; Humans; Induced Pluripotent Stem Cells; Lateral Ventricles; Mice; Mice, Inbred C57BL; Models, Animal; Neocortex; Neural Stem Cells; Neuroglia
PubMed: 34728600
DOI: 10.1038/s41467-021-26447-w -
Cells & Development Jun 2023In the adult rodent brain, neural stem cells (NSCs) reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus.... (Review)
Review
In the adult rodent brain, neural stem cells (NSCs) reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampus. In these areas, NSCs and their progeny integrate intrinsic signals and extrinsic cues provided by their microenvironment that control their behavior. The vasculature in the SVZ and SGZ, and the choroid plexus (ChP) in the SVZ, have emerged as critical compartments of the neurogenic niches as they provide a rich repertoire of cues to regulate NSC quiescence, proliferation, self-renewal and differentiation. Physical contact between NSCs and blood vessels is also a feature within the niches and supports different processes such as quiescence, migration and vesicle transport. In this review, we provide a description of the brain and choroid plexus vasculature in both stem cell niches, highlighting the main properties and role of the vasculature in each niche. We also summarize the current understanding of how blood vessel- and ChP-derived signals influence the behavior of NSCs in physiological adulthood, as well as upon aging.
Topics: Neural Stem Cells; Neurogenesis; Brain; Lateral Ventricles; Cell Differentiation
PubMed: 37060947
DOI: 10.1016/j.cdev.2023.203841 -
Journal of Neuro-oncology Jan 2017The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether... (Meta-Analysis)
Meta-Analysis Review
The ventricular-subventricular zone (V-SVZ), which lies in the walls of the lateral ventricles (LV), is the largest neurogenic niche within the adult brain. Whether radiographic contact with the LV influences survival in glioblastoma (GBM) patients remains unclear. We assimilated and analyzed published data comparing survival in GBM patients with (LV+GBM) and without (LV-GBM) radiographic LV contact. PubMed, EMBASE, and Cochrane electronic databases were searched. Fifteen studies with survival data on LV+GBM and LV-GBM patients were identified. Their Kaplan-Meier survival curves were digitized and pooled for generation of median overall (OS) and progression free (PFS) survivals and log-rank hazard ratios (HRs). The log-rank and reported multivariate HRs after accounting for the common predictors of GBM survival were analyzed separately by meta-analyses. The calculated median survivals (months) from pooled data were 12.95 and 16.58 (OS), and 4.54 and 6.25 (PFS) for LV+GBMs and LV-GBMs, respectively, with an overall log-rank HRs of 1.335 [1.204-1.513] (OS) and 1.387 [1.225-1.602] (PFS). Meta-analysis of log-rank HRs resulted in summary HRs of 1.58 [1.35-1.85] (OS, 10 studies) and 1.41 [1.22-1.64] (PFS, 5 studies). Meta-analysis of multivariate HRs resulted in summary HRs of 1.35 [1.14-1.58] (OS, 6 studies) and 1.64 [0.88-3.05] (PFS, 3 studies). Patients with GBM contacting the LV have lower survival. This effect may be independent of the common predictors of GBM survival, suggesting a clinical influence of V-SVZ contact on GBM biology.
Topics: Brain Neoplasms; Disease Progression; Glioblastoma; Humans; Kaplan-Meier Estimate; Lateral Ventricles
PubMed: 27644688
DOI: 10.1007/s11060-016-2278-7 -
Cells Sep 2022Neural stem cells (NSCs) are self-renewing, multipotent cells which give rise to all components of the central nervous system (CNS) during embryogenesis, but also... (Review)
Review
Neural stem cells (NSCs) are self-renewing, multipotent cells which give rise to all components of the central nervous system (CNS) during embryogenesis, but also activate in response to injury and disease and maintain a certain level of neurogenic activity throughout adulthood. This activity takes place in specialized regions of the brain, the neurovascular niches, whose main role is to control the behaviour of the CNS. In adult mammals, two main "canonical" niches have been described: The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. This review discusses our current understanding of the neural stem cells and their canonical niches, as well as their structure, behaviours, and role in neural disease.
Topics: Animals; Lateral Ventricles; Mammals; Multipotent Stem Cells; Neural Stem Cells; Neurogenesis; Stem Cell Niche
PubMed: 36230964
DOI: 10.3390/cells11193002