Article

Aging of the subventricular zone neural stem cell niche.

Department of Physiology and Neurobiology
Aging and disease 02/2011; 2(1):49-63.
Source: PubMed

ABSTRACT The persistence of an active subventricular zone neural stem cell niche in the adult mammalian forebrain supports its continued role in the production of new neurons and in generating cells to function in repair through adulthood. Unfortunately, with increasing age the niche begins to deteriorate, compromising these functions. The reasons for this decline are not clear. Studies are beginning to define the molecular and physiologic changes in the microenvironment of the aging subventricular zone niche. New revelations from aging studies will allow for a more thorough understanding of which reparative functions are lost in the aged brain, the progression of niche demise and the possibility for therauptic intervention to improve aging brain function.

Download full-text

Full-text

Available from: Joanne Conover, Jul 02, 2015
1 Follower
 · 
96 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: After an ischemic stroke, neural precursor cells (NPCs) proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate toward the ischemic lesion where they promote tissue remodeling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurolog-ical functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complement-ing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood–brain barrier integrity. On the contrary, local stem cell delivery allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response. Herein we describe the diverse capabilities of exogenous (systemically vs. locally transplanted) NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors' claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.
    Frontiers in Cellular Neuroscience 09/2014; 8. DOI:10.3389/fncel.2014.00291 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The link between neuroinflammation and neurogenesis is an area of intensive research in contemporary neuroscience. The burgeoning amount of evidence accumulated over the past decade has been incredible, and now there remains the figuring out of minutia to give us a more complete picture of what individual, synergistic, and antagonistic events are occurring between neurogenesis and neuroinflammation. An intricate study of the inflammatory microenvironment influenced by the presence of the various inflammatory components like cytokines, chemokines, and immune cells is essential for: 1) understanding how neurogenesis can be affected in such a specialized niche and 2) applying the knowledge gained for the treatment of cognitive and/or motor deficits arising from inflammation-associated diseases like stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease. This review is written to provide the reader with up-to-date information explaining how these inflammatory components are effecting changes on neurogenesis.
    Metabolic Brain Disease 03/2014; 30(2). DOI:10.1007/s11011-014-9523-6 · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Age-associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricle surface gliosis is associated with ventriculomegaly. To examine whether loss of ependymal cell coverage resulting in ventricle surface glial scarring can lead directly to ventricle enlargement independent of any other injury or degenerative loss, we modeled in mice the glial scarring found along the lateral ventricle surface in aged humans. Neuraminidase, which cleaves glycosidic linkages of apical adherens junction proteins, was administered intracerebroventricularly to denude areas of ependymal cells. Substantial ependymal cell loss resulted in reactive gliosis rather than stem cell-mediated regenerative repair of the ventricle lining, and the gliotic regions showed morphologic and phenotypic characteristics similar to those found in aged humans. Increased levels of aquaporin-4, indicative of edema, observed in regions of periventricular gliosis in human tissue were also replicated in our mouse model. 3D modeling together with volume measurements revealed that mice with ventricle surface scarring developed expanded ventricles, independent of neurodegeneration. Through a comprehensive, comparative analysis of the lateral ventricles and associated periventricular tissue in aged humans and mouse, followed by modeling of surface gliosis in mice, we have demonstrated a direct link between lateral ventricle surface gliosis and ventricle enlargement. These studies highlight the importance of maintaining an intact ependymal cell lining throughout aging.
    Aging cell 12/2013; DOI:10.1111/acel.12184 · 5.94 Impact Factor