Gui Zhang

University of Texas Southwestern Medical Center, Dallas, TX, United States

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Publications (4)23.83 Total impact

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    ABSTRACT: Many genes regulating adult neurogenesis have been identified and are known to play similar roles during early neuronal development. We recently identified apolipoprotein E (ApoE) as a gene the expression of which is essentially absent in early brain progenitors but becomes markedly upregulated in adult dentate gyrus stem/progenitor cells. Here, we demonstrate that ApoE deficiency impairs adult dentate gyrus development by affecting the neural progenitor pool over time. We utilized ApoE-deficient mice crossed to a nestin-GFP reporter to demonstrate that dentate gyrus progenitor cells proliferate more rapidly at early ages, which is subsequently accompanied by an overall decrease in neural progenitor cell number at later time points. This appears to be secondary to over-proliferation early in life and ultimate depletion of the Type 1 nestin- and GFAP-expressing neural stem cells. We also rescue the proliferation phenotype with an ApoE-expressing retrovirus, demonstrating that ApoE works directly in this regard. These data provide novel insight into late hippocampal development and suggest a possible role for ApoE in neurodegenerative diseases.
    Development 08/2011; 138(20):4351-62. · 6.60 Impact Factor
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    ABSTRACT: Significant spontaneous recovery occurs after essentially all forms of serious brain injury, although the mechanisms underlying this recovery are unknown. Given that many forms of brain injury such as traumatic brain injury (TBI) induce hippocampal neurogenesis, we investigated whether these newly generated neurons might play a role in recovery. By modeling TBI in transgenic mice, we determined that injury-induced newly generated neurons persisted over time and elaborated extensive dendritic trees that stably incorporated themselves throughout all neuronal layers of the dentate gyrus. When we selectively ablated dividing stem/progenitors at the time of injury with ganciclovir in a nestin-HSV-TK transgenic model, we eliminated injury-induced neurogenesis and subsequently diminished the progenitor pool. Moreover, using hippocampal-specific behavioral tests, we demonstrated that only injured animals with neurogenesis ablated at the time of injury lost the ability to learn spatial memory tasks. These data demonstrate a functional role for adult neurogenesis after brain injury and offer compelling and testable therapeutic options that might enhance recovery.
    Journal of Neuroscience 03/2011; 31(13):4906-16. · 6.91 Impact Factor
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    ABSTRACT: Brain remodeling occurs after all forms of brain injury, though the mechanisms underlying this phenomenon are mostly unknown. Neural stem and progenitor cells are one source of endogenous cells that may contribute to brain remodeling and subsequent recovery. In addition, certain populations of progenitors are particularly susceptible to injury, and their depletion may lead to the impairment of developmental processes that vary with age. We particularly focus on glial progenitors, which are more abundant postnatally and particularly susceptible to acquired brain injuries such as traumatic brain injury. We have recently characterized a novel transgenic mouse that expresses herpes thymidine kinase under the control of the neural-progenitor-specific nestin promoter and allows for temporally induced ablation of dividing progenitors. By genetically depleting dividing cortical progenitors at various times, we identify postnatal day 7 (P7) to P14 as a critical period for oligodendrogenesis. Targeted ablation of dividing progenitors during this window leads to cell-specific depletion of oligodendrocyte precursors expressing platelet-derived growth factor receptor-α and corresponding myelination and motor deficits. This modeling provides insight into how the age at which white matter injury occurs influences both injury severity and subsequent recovery.
    Developmental Neuroscience 01/2010; 32(5-6):499-509. · 3.41 Impact Factor
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    ABSTRACT: It is becoming increasingly clear that brain injuries from a variety of causes stimulate neurogenesis within the hippocampus. It remains unclear, however, how robust this response may be and what primary cell types are involved. Here, using a controlled cortical impact model of traumatic brain injury on a previously characterized transgenic mouse line that expresses enhanced green fluorescent protein (eGFP) under the control of the nestin promoter, we demonstrate that it is the earliest type-1 quiescent progenitor cells that are induced to proliferate and migrate outside the subgranular layer of the dentate gyrus. This type-1 cell activation occurs at the same time that we observe adjacent but more differentiated doublecortin-expressing progenitors (type-2 cells) being eliminated. Also, although type-2 cells remain intact in the contralateral (uninjured) dentate gyrus, the type-1 cells there are also activated and result in increased numbers of the doublecortin-expressing type-2 cells. In addition, we have generated a novel mouse transgenic that expresses a modified version of the herpes simplex virus thymidine kinase along with eGFP that allows for the visualization and inducible ablation of early dividing progenitors by exposing them to ganciclovir. Using this transgenic in the context of traumatic brain injury, we demonstrate that these early progenitors are required for injury-induced remodeling to occur. This work suggests that injury-induced hippocampal remodeling following brain injury likely requires sustained activation of quiescent early progenitors.
    Journal of Neuroscience 12/2008; 28(48):12901-12. · 6.91 Impact Factor