A novel flow cytometry‐based technique to measure adult neurogenesis in the brain

Spoelgen, Robert; Meyer, A; Moraru, Anja; Kirsch, Friederike; Vogt-Eisele, Angela; Plaas, Christian; Pitzer, Claudia; Schneider, Armin

doi:10.1111/j.1471-4159.2011.07413.x

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…Cell nuclei were purified and immunotagged with neuronal NeuN antibody, which allows for separate counting and collection of (neuronal) NeuN + and (glial and other non-neuronal) NeuN − nuclei (Figure 2A–E). This approach is increasingly used to rapidly quantify numbers of neuronal and non-neuronal nuclei in mammalian brains(Herculano-Houzel et al, 2015; Spoelgen et al, 2011), and bypasses many of the limitations associated with two- and three-dimensional cell counting techniques in histological material which face inherent limitations particularly for sparsely occurring cell populations such as the WMN(Benes and Lange, 2001; Herculano-Houzel et al, 2015). The three treatment groups did not differ significantly in the total number of white matter nuclei sorted.…”

Section: Resultsmentioning

confidence: 99%

NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

Halene

Kozlenkov

Jiang

et al. 2016

Schizophrenia Research

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Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted.

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Section: Resultsmentioning

confidence: 99%

NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

Halene

Kozlenkov

Jiang

et al. 2016

Schizophrenia Research

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“…Current standard methods for monitoring adult neurogenesis are based on a retrospective analysis of post mortem tissue4445. The first report on human adult neurogenesis used brain samples from patients with cancer who had received a single injection of BrdU for diagnostic purposes3.…”

Section: Discussionmentioning

confidence: 99%

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

Lugert

Kremer

Jagasia

et al. 2017

Sci Rep

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Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.

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“…A similar procedure was completed with isolation of the striatum, but yielded similar results; therefore the entire hemisphere was used to increase the number of counts per sample. The following method has been optimized from studies previously described and validated354950. The brain was diced into small pieces and suspended in 4 ml of PBS.…”

Section: Methodsmentioning

confidence: 99%

Surface chemistry governs cellular tropism of nanoparticles in the brain

et al. 2017

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Nanoparticles are of long-standing interest for the treatment of neurological diseases such as glioblastoma. Most past work focused on methods to introduce nanoparticles into the brain, suggesting that reaching the brain interstitium will be sufficient to ensure therapeutic efficacy. However, optimized nanoparticle design for drug delivery to the central nervous system is limited by our understanding of their cellular deposition in the brain. Here, we investigated the cellular fate of poly(lactic acid) nanoparticles presenting different surface chemistries, after administration by convection-enhanced delivery. We demonstrate that nanoparticles with ‘stealth' properties mostly avoid internalization by all cell types, but internalization can be enhanced by functionalization with bio-adhesive end-groups. We also show that association rates measured in cultured cells predict the extent of internalization of nanoparticles in cell populations. Finally, evaluating therapeutic efficacy in an orthotopic model of glioblastoma highlights the need to balance significant uptake without inducing adverse toxicity.

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A novel flow cytometry‐based technique to measure adult neurogenesis in the brain

Cited by 12 publications

References 29 publications

NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

NeuN+ neuronal nuclei in non-human primate prefrontal cortex and subcortical white matter after clozapine exposure

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

Surface chemistry governs cellular tropism of nanoparticles in the brain

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