Adaptive Roles of Programmed Cell Death During Nervous System Development

Buss, Robert R.; Sun, Woong; Oppenheim, Ronald W.

doi:10.1146/annurev.neuro.29.051605.112800

Cited by 350 publications

(288 citation statements)

References 311 publications

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“…Apoptosis is an integral part of neural development [40][41][42][43] in vivo and a common feature of neural differentiation in vitro [41]. We observed a significant amount of cell death during NP cell-based neuronal differentiation, however, NP cells differentiated in LIF þ medium showed significantly lower number of TUNEL positive apoptotic cells (Fig.…”

Section: Reduced Apoptosis Correlated To Reduction In Caspases and Rosmentioning

confidence: 69%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

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Various growth factor cocktails have been used to proliferate and then differentiate human neural progenitor (NP) cells derived from embryonic stem cells (ESC) for in vitro and in vivo studies. However, the cytokine leukemia inhibitory factor (LIF) has been largely overlooked. Here, we demonstrate that LIF significantly enhanced in vitro survival and promoted differentiation of human ESC-derived NP cells. In NP cells, as well as NP-derived neurons, LIF reduced caspase-mediated apoptosis and reduced both spontaneous and H 2 O 2 -induced reactive oxygen species in culture. In vitro, NP cell proliferation and the yield of differentiated neurons were significantly higher in the presence of LIF. In NP cells, LIF enhanced cMyc phosphorylation, commonly associated with self-renewal/proliferation. Also, in differentiating NP cells LIF activated the phosphoinositide 3-kinase and signal transducer and activator of transcription 3 pathways, associated with cell survival and reduced apoptosis. When differentiated in LIF 1 media, neurite outgrowth and ERK1/2 phosphorylation were potentiated together with increased expression of gp130, a component of the LIF receptor complex. NP cells, pretreated in vitro with LIF, were effective in reducing infarct volume in a model of focal ischemic stroke but LIF did not lead to significantly improved initial NP cell survival over nontreated NP cells. Our results show that LIF signaling significantly promotes human NP cell proliferation, survival, and differentiation in vitro. Activated LIF signaling should be considered in cell culture expansion systems for future human NP cell-based therapeutic transplant studies.

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Section: Reduced Apoptosis Correlated To Reduction In Caspases and Rosmentioning

confidence: 69%

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

et al. 2012

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“…According to the neurotrophic hypothesis (Oppenheim 1989), neurons that establish effective connections are able to obtain more neurotrophic factor and are more likely to survive. Thus one important function of cell death in brain development is its role in regulating the establishment of effective and functional neural circuits (Buss et al 2006). In addition, a number of other functions for cell death have been proposed.…”

Section: Regressive Events In Prenatal Brain Developmentmentioning

confidence: 99%

The Basics of Brain Development

Stiles¹,

Reilly²,

Levine³

et al. 2012

Neural Plasticity and Cognitive Development

134

150

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“…Table 2 and Table 4 rons with non-functional synapses are eliminated during the normal development process through neuroapoptosis [6] . On the other hand, neuroapoptosis also plays an important role in clearing away sick cells in neurodegenerative disease [7] .…”

Section: Correlation Between Caspase-3 Activation and Nf-κb Activitymentioning

confidence: 99%

Expression of the apoptosis-related proteins caspase-3 and NF-κB in the hippocampus of Tg2576 mice

Niu

Zhang

et al. 2010

Neurosci. Bull.

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Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer's disease (AD), especially the role of NF-κB in the regulation of neuroapoptosis. Methods expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF-κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 (P < 0.01 or P < 0.05). Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.

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Adaptive Roles of Programmed Cell Death During Nervous System Development

Cited by 350 publications

References 311 publications

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

Neurotrophic Effects of Leukemia Inhibitory Factor on Neural Cells Derived from Human Embryonic Stem Cells

The Basics of Brain Development

Expression of the apoptosis-related proteins caspase-3 and NF-κB in the hippocampus of Tg2576 mice

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