The SVZ and Its Relationship to Stem Cell Based Neuro-oncogenesis

Kusne, Yael; Sanai, Nader

doi:10.1007/978-3-319-16537-0_2

Cited by 13 publications

(8 citation statements)

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“…However, in the mouse some experimental models have also generated gliomas from mature progenitors, arguing that the V-SVZ may not be an obligate site of origin [34–36]. Computer models of glioma growth based on MRI sequences suggest that sites of origins of GBMs are widely distributed throughout the brain and not limited to the V-SVZ [37].…”

Section: Discussionmentioning

confidence: 99%

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

et al. 2016

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“…Moreover, the role of the SVZ neurogenic niche in the formation and propagation of brain tumors have been tackled and, as expected, SVZ-NSPCs transformation was correlated with loss of function of cell cycle proteins, typically tumor suppressor genes e.g., p53, Rb, Pten, and NF1. Thus, it was proposed that SVZ-NSCs/NPCs could be the initiating cells during gliomagenesis based on several shared features with tumor cells such as multipotency, expression of stem cell markers e.g., Sox2 and Nestin, and, responsiveness to extrinsic signals e.g., Sonic Hedgehog (Kusne and Sanai, 2015 ). For instance, following the exposure of p53 −/− mice to the mutagen n -ethyl- n -nitrosourea (ENU), glioblastoma-like tumors can form in periventricular locations and are characterized by enhanced NSCs self-renewal, recruitment to the fast-proliferating progenitor population (type C) and impaired differentiation (Gil-Perotin et al, 2006 ).…”

Section: Cell Cycle Control In the Adult Svz-ob Olfactory Dysfunctiomentioning

confidence: 99%

“Till Death Do Us Part”: A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

2018

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Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival. Importantly, aberrant cell cycle re-entry (CCE) in post-mitotic neurons has been strongly linked to the abnormal pathophysiology in rodent models of neurodegenerative diseases with potential implications on the etiology and progression of such diseases in humans. Here, we present an overview of AN in the SVZ-OB and olfactory epithelium (OE) in mice and humans followed by a comprehensive update of the distinct roles played by cell cycle proteins including major tumors suppressor genes in various steps during neurogenesis. We also discuss accumulating evidence underlining a strong link between abnormal cell cycle control, olfactory dysfunction and neurodegeneration in the adult and aging brain. We emphasize that: (1) CCE in post-mitotic neurons due to loss of cell cycle suppression and/or age-related insults as well as DNA damage can anticipate the development of neurodegenerative lesions and protein aggregates, (2) the age-related decline in SVZ and OE neurogenesis is associated with compensatory pro-survival mechanisms in the aging OB which are interestingly similar to those detected in Alzheimer's disease and Parkinson's disease in humans, and (3) the OB represents a well suitable model to study the early manifestation of age-related defects that may eventually progress into the formation of neurodegenerative lesions and, possibly, spread to the rest of the brain. Such findings may provide a novel approach to the modeling of neurodegenerative diseases in humans from early detection to progression and treatment as well.

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“…The proper turnover enforced by proliferation, migration as well as apoptosis in the OB, is essential for optimizing olfaction [( 11 ); Figure 1 ]. Therefore, the study of V-SVZ is capital for many purposes: understanding unregulated cell growth in tumor formations ( 12 , 13 ), preventing or replacing cell loss in aging ( 1 , 14 , 15 ), decreasing neurodegenerative disease risks ( 16 – 18 ), and improving stroke treatments ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Sex Steroids and Adult Neurogenesis in the Ventricular-Subventricular Zone

2018

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The forebrain ventricular-subventricular zone (V-SVZ) continuously generates new neurons throughout life. Neural stem cells (type B1 cells) along the lateral ventricle become activated, self-renew, and give rise to proliferating precursors which progress along the neurogenic lineage from intermediate progenitors (type C cells) to neuroblasts (type A cells). Neuroblasts proliferate and migrate into the olfactory bulb and differentiate into different interneuronal types. Multiple factors regulate each step of this process. Newly generated olfactory bulb interneurons are an important relay station in the olfactory circuits, controlling social recognition, reproductive behavior, and parental care. Those behaviors are strongly sexually dimorphic and changes throughout life from puberty through aging and in the reproductive age during estrous cycle and gestation. Despite the key role of sex hormones in regulating those behaviors, their contribution in modulating adult neurogenesis in V-SVZ is underestimated. Here, we compare the literature highlighting the sexual dimorphism and the differences across the physiological phases of the animal for the different cell types and steps through the neurogenic lineage.

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The SVZ and Its Relationship to Stem Cell Based Neuro-oncogenesis

Cited by 13 publications

References 50 publications

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

Influence of glioblastoma contact with the lateral ventricle on survival: a meta-analysis

“Till Death Do Us Part”: A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb

Sex Steroids and Adult Neurogenesis in the Ventricular-Subventricular Zone

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