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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 -
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 -
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 -
Scientific Reports Sep 2018We utilized three-dimensional, surface-based, morphometric analysis to investigate ventricle shape between 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH)... (Clinical Trial)
Clinical Trial
We utilized three-dimensional, surface-based, morphometric analysis to investigate ventricle shape between 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims were (1) to evaluate the location of INPH-related structural abnormalities of the lateral ventricles and (2) to investigate relationships between lateral ventricular enlargement and cortical thinning in INPH patients. Thirty-three INPH patients and 23 healthy controls were included in this study. We used sparse canonical correlation analysis to show correlated regions of ventricular surface expansion and cortical thinning. Significant surface expansion in the INPH group was observed mainly in clusters bilaterally located in the superior portion of the lateral ventricles, adjacent to the high convexity of the frontal and parietal regions. INPH patients showed a significant bilateral expansion of both the temporal horns of the lateral ventricles and the medial aspects of the frontal horns of the lateral ventricles to surrounding brain regions, including the medial frontal lobe. Ventricular surface expansion was associated with cortical thinning in the bilateral orbitofrontal cortex, bilateral rostral anterior cingulate cortex, left parahippocampal cortex, left temporal pole, right insula, right inferior temporal cortex, and right fusiform gyrus. These results suggest that patients with INPH have unique patterns of ventricular surface expansion. Our findings encourage future studies to elucidate the underlying mechanism of lateral ventricular morphometric abnormalities in INPH patients.
Topics: Aged; Female; Frontal Lobe; Humans; Hydrocephalus, Normal Pressure; Lateral Ventricles; Magnetic Resonance Imaging; Male; Parietal Lobe; Prospective Studies
PubMed: 30190599
DOI: 10.1038/s41598-018-31399-1 -
Journal of Neuroinflammation Sep 2022Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More...
Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in Alzheimer's disease.
BACKGROUND
Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD.
METHODS
In this study, we constructed AD model mice by injecting Aβ into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group.
RESULTS
Aβ i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ treatment group.
CONCLUSIONS
The present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; DNA, Ribosomal; Dysbiosis; Gastrointestinal Microbiome; Lateral Ventricles; Mice; Neurodegenerative Diseases; Neuroimmunomodulation
PubMed: 36171620
DOI: 10.1186/s12974-022-02599-4 -
Psychiatry Research. Neuroimaging Jun 2016Studies on structural brain abnormalities in individuals with autism spectrum disorders (ASD) have been of limited size and many findings have not been replicated. In...
Studies on structural brain abnormalities in individuals with autism spectrum disorders (ASD) have been of limited size and many findings have not been replicated. In the largest ASD brain morphology study to date, we compared subcortical, total brain (TBV), and intracranial (ICV) volumes between 472 subjects with DSM-IV ASD diagnoses and 538 healthy volunteers (age range: 6-64 years), obtained from high-resolution structural brain scans provided by the Autism Brain Imaging Data Exchange (ABIDE). Compared to healthy volunteers, we found significantly larger pallidum (Cohen's d=0.15) and lateral ventricle volumes (Cohen's d=0.18) in ASD. These enlargements were independent of total brain volume and IQ, passed FDR correction for multiple comparisons, and were observed in overall, male-only, and medication-free subjects. In addition, intracranial, hippocampal, and caudate volumes were enlarged in ASD at a nominal statistical threshold of p<0.05. This study provides the first robust evidence for pallidum enlargement in ASD independent from TBV and encourages further study of the functional role of the pallidum in individuals with autism spectrum disorder.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Brain; Case-Control Studies; Child; Female; Globus Pallidus; Hippocampus; Humans; Intelligence; Lateral Ventricles; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Young Adult
PubMed: 27179315
DOI: 10.1016/j.pscychresns.2016.04.003 -
Stem Cells Translational Medicine Apr 2020
Review
Topics: Apoptosis; Carcinogenesis; Exosomes; Humans; Lateral Ventricles; Neurogenesis; Stem Cell Transplantation
PubMed: 32227467
DOI: 10.1002/sctm.20-0095