Neuronal cell death: searching for the smoking gun

Pittman, Randall N.; Mills, Jason C.; DiBenedetto, Angela J.; Hynicka, Weslia P; Wang, Songli

doi:10.1016/0959-4388(94)90036-1

Cited by 21 publications

(10 citation statements)

References 50 publications

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“…They exhibit partially overlapping but distinct patterns of signal activation and spatial distribu tion, and target a diversity of neuronal cell types. NGF signals through the high-affinity Trk A receptor [24,25], In vitro, NGF promotes neurite outgrowth and survival of sensory and sympathetic, neurons, while in vivo it attenuates naturally occurring death in developing sym pathetic and dorsal root ganglia [22,26,27], In the cen tral nervous system (CNS), NGF exhibits limited tran script expression, with the highest levels present in developing and adult hippocampal CA pyramidal and dentate gyrus granule neurons [28]. In the developing forebrain and in the hippocampus, striatum and hypo thalamus, subsets of neurons expresses transcripts for NGF and Trk A, with colocalization occurring within some neuronal supopulations [29].…”

Section: Nerve Growth Factor and Trk Amentioning

confidence: 99%

Growth Factor Regulation of Neuronal Development

Mehler

Kessler

1994

Dev Neurosci

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Recent experimental investigations have redefined the spectrum of growth factors and developmental signalling pathways that are necessary to orchestrate the growth and differentiation of regional neuronal subpopulations. Gene knockout studies of the classic neurotrophins and their high-affinity tyrosine kinase (Trk) receptors have refined our definition of the cellular mechanisms and target populations of these neuronotrophic factors. Recognition of the significant parallels that exist between neuropoiesis and hematolymphopoiesis has fostered our study of the range and cellular actions of these hemopoietins in neuronal development. In addition, by activating receptor subunits that possess serine/threonine activity, bone morphogenetic proteins of the transforming growth factor-β superfamily exhibit complex spatiotemporal regulation of regional neuronal subpopulations. These collective observations suggest that a complex hierarchy of epigenetic signals is required for the growth and maturation of regional neuronal lineage species in the central and peripheral mammalian nervous system.

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Section: Nerve Growth Factor and Trk Amentioning

confidence: 99%

Growth Factor Regulation of Neuronal Development

Mehler

Kessler

1994

Dev Neurosci

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“…The time course of transcription factor expression in tissues undergoing apoptosis, as well as the effect of transcription and translation inhibitors on neuronal injury, suggest that some transcription factors may participate in the regulation of the destructive process (Pittman et al, 1994;Hughes et al, 1997). One such transcription factor is nuclear factor B (NF-B).…”

mentioning

confidence: 99%

Nuclear Factor κB Nuclear Translocation Upregulates c-Myc and p53 Expression during NMDA Receptor-Mediated Apoptosis in Rat Striatum

Qin¹,

Chen

Wang³

et al. 1999

J. Neurosci.

226

182

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Nuclear factor B (NF-B) appears to participate in the excitotoxin-induced apoptosis of striatal medium spiny neurons. To elucidate molecular mechanisms by which this transcription factor contributes to NMDA receptor-triggered apoptotic cascades in vivo, rats were given the NMDA receptor agonist quinolinic acid (QA) by intrastriatal infusion, and the role of NF-B in the induction of apoptosis-related genes and gene products was evaluated. QA administration induced timedependent NF-B nuclear translocation. The nuclear NF-B protein after QA treatment was comprised mainly of p65 and c-Rel subunits as detected by gel supershift assay. Levels of c-Myc and p53 mRNA and protein were markedly increased at the time of QA-induced NF-B nuclear translocation. Immunohistochemical analysis showed that c-Myc and p53 induction occurred in the excitotoxin-sensitive medium-sized striatal neurons. NF-B nuclear translocation was blocked in a dosedependent manner by the cell-permeable recombinant peptide NF-B SN50, but not by the NF-B SN50 control peptide. NF-B SN50 significantly inhibited the QA-induced elevation in levels of c-Myc and p53 mRNA and protein. Pretreatment or posttreatment with NF-B SN50, but not the control peptide, also substantially reduced the intensity of QA-induced internucleosomal DNA fragmentation. The results suggest that NF-B may promote an apoptotic response in striatal medium-sized neurons to excitotoxic insult through upregulation of c-Myc and p53. This study also provides evidence indicating an unique signaling pathway from the cytoplasm to the nucleus, which regulates p53 and c-Myc levels in these neurons during apoptosis.

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“…PCD is also seen earlier in development, prior to terminal differentiation (Raff et al 1993;Pittman et al 1994) in several areas, including the retina, the optic tectum (Cantino 1972), sensory ganglia (Oppenheim 1991), the spinal cord (Carr and Simpson 1982;Lance-Jones 1982;Homma et al 1994), and the telencephalon (Smart and McSherry 1982;Ferrer et al 1992;Acklin and van der Kooy 1993), and is associated with various morphogenetic movements such as closure of the neural tube (Weil et al 1997) and the formation of the corpus callosum. While the determinants of survival and death in these situations are poorly understood, in each case, cell death is restricted to defined cell populations.…”

Section: Introductionmentioning

confidence: 97%

Mutations resulting in transient and localized degeneration in the developing zebrafish brain

Rodriguez

Driever²

1997

Biochem. Cell Biol.

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In a large-scale mutagenesis screen in the zebrafish, Danio rerio, we have identified a heterogeneous group of 30 recessive, embryonic lethal mutations characterized by degeneration in the developing central nervous system that is either transient or initially localized to one area of the brain. Transient degeneration is defined as abnormal cell death occurring during a restricted period of development. Following degeneration, the affected structures do not appear to regenerate. In each case degeneration is identified after somitogenesis is complete and is not associated with visually identified patterning defects. These 30 mutations, forming 21 complementation groups, have been classified into four phenotypic groups: group 1, transient degeneration (13 mutations); group 2, spreading degeneration, early onset, in which degeneration is initially confined to the optic tectum but subsequently spreads to other areas of the central nervous system (7 mutations); group 3, late-onset degeneration, initially identified after 4 days (6 mutations); and group 4, degeneration with abnormal pigmentation (4 mutations). Although apoptotic cells are seen in the retina and tectum of all mutants, the distribution, temporal progression, and severity of degeneration vary between mutations. Several mutations also show pleiotropic effects, with degeneration involving extraneural structures including the pharyngeal arches and pectoral fins. We discuss some of the pathways important for cell survival in the nervous system and suggest that these mutations will provide entry points for identifying genes that affect the survival of restricted neural populations.

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Neuronal cell death: searching for the smoking gun

Cited by 21 publications

References 50 publications

Growth Factor Regulation of Neuronal Development

Growth Factor Regulation of Neuronal Development

Nuclear Factor κB Nuclear Translocation Upregulates c-Myc and p53 Expression during NMDA Receptor-Mediated Apoptosis in Rat Striatum

Mutations resulting in transient and localized degeneration in the developing zebrafish brain

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