Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation

Rami, Abdelhaq; Jansen, Susan A.; Giesser, I.; Winckler, J.

doi:10.1016/s0197-0186(03)00002-0

Cited by 39 publications

(29 citation statements)

References 47 publications

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“…Zinc deficiencyinduced apoptosis is dependent on caspase 3 activation (57). Activated caspase 3 has been reported in axons (including mossy fibers) and dendrites in the HC following ischemia, when zinc levels are decreased in mossy fibers (36,46). In NBD, we found increased levels of activated caspase 3 in nuclei, mossy fibers, and dendrites of DGNs in association with decreased levels of zinc in mossy fibers.…”

Section: Discussionsupporting

confidence: 56%

Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection

Williams

Hornig

Yaddanapudi

et al. 2008

J Virol

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Infection of neonatal rats with Borna disease virus results in a characteristic behavioral syndrome and apoptosis of subsets of neurons in the hippocampus, cerebellum, and cortex (neonatal Borna disease [NBD]).In the NBD rat hippocampus, dentate gyrus granule cells progressively degenerate. Apoptotic loss of granule cells in NBD is associated with accumulation of zinc in degenerating neurons and reduced zinc in granule cell mossy fibers. Excess zinc can trigger poly(ADP-ribose) polymerase 1 (PARP-1) activation, and PARP-1 activation can mediate neuronal death. Here, we evaluate hippocampal PARP-1 mRNA and protein expression levels, activation, and cleavage, as well as apoptosis-inducing factor (AIF) nuclear translocation and executioner caspase 3 activation, in NBD rats. PARP-1 mRNA and protein levels were increased in NBD hippocampi. PARP-1 expression and activity were increased in granule cell neurons and glia with enhanced ribosylation of proteins, including PARP-1 itself. In contrast, levels of poly(ADP-ribose) glycohydrolase mRNA were decreased in NBD hippocampi. PARP-1 cleavage and AIF expression were also increased in astrocytes in NBD hippocampi. Levels of activated caspase 3 protein were increased in NBD hippocampi and localized to nuclei, mossy fibers, and dendrites of granule cell neurons. These results implicate aberrant zinc homeostasis, PARP-1, and caspase 3 activation as contributing factors in hippocampal neurodegeneration in NBD.Borna disease virus (BDV) is a nonsegmented, negativesense, single-stranded RNA virus that persistently infects the central nervous systems (CNS) of and causes behavioral disturbances in a wide range of mammalian and avian species (18,25). Experimental infection of adult immunocompetent Lewis rats causes a severe meningoencephalitis and a progressive movement disorder that may be associated with detected alterations of the dopamine system and immune-mediated damage (29, 52). In contrast, newborn rats infected with BDV (neonatal borna disease [NBD]) do not mount an overt cellular immune response yet have prominent neuronal loss; pronounced astrogliosis and microgliosis; altered cytokine, neurotrophic factor, and neurotrophic factor receptor gene expression; abnormal development of brain monoaminergic systems; neuronal and astrocytic endoplasmic reticulum (ER) stress; and disturbances of learning, mood, and behavior (11,31,38,45,62,67). Although BDV is noncytolytic, NBD is attended by apoptotic degeneration of neurons that undergo substantial postnatal maturation, especially in the hippocampus (HC), cerebellum (CBLM), and cortex (31, 60). Neuronal loss in the CBLM is associated with the induction of ER stress in Purkinje cells, expression of the proapototic molecule C/EBP homologous protein (CHOP), and deficient expression of ER quality control molecules. However, apoptosis of HC dentate gyrus granule cell neurons (DGNs) is not associated with the clear signs of ER disturbances found in other brain regions (62). Thus, the molecular mechanisms contributing to HC neurodegene...

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Section: Discussionsupporting

confidence: 56%

Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection

Williams

Hornig

Yaddanapudi

et al. 2008

J Virol

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“…2), might be recruited as part of the death process or alternatively become activated as incidental bystanders. 35,[37][38][39][40] Others and we have demonstrated the activation of downstream caspase-3 is a crucial event in neuronal death following global and focal ischemia in the brain. 39,40,35 Figure 1C shows an example of neuronal caspase-3 activation in the ischemic penumbra after focal cerebral ischemia in rats detected by using an antibody that recognizes only the activated form of caspase-3.…”

Section: Evidence Of Apoptotic Neuronal Death In the Penumbramentioning

confidence: 75%

Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin?

Rami

Kögel²

2008

Autophagy

122

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Autophagy is a homeostatic cellular process required for the recycling of proteins and damaged organelles, and in most scenarios is believed to promote cell survival. However, there is accumulating evidence that under certain pathological situations, autophagy can also trigger and mediate programmed cell death (type II death). Despite the well-established pathophysiological role of apoptosis (type I cell death) in post-ischemic neuron death, there is now increasing interest whether alternative types of programmed cell death might be involved in regulation of neuronal death after both global and focal cerebral ischemia. Initial studies demonstrating the involvement of lysosomal proteases of the cathepsin family in neuron death after global ischemia already had suggested that this type of cell death may occur in an autophagy-dependent manner. Recently it was also shown that focal ischemia is associated with potently enhanced expression of the autophagy regulator Beclin 1 and subcellular redistribution of the autophagic marker LC3 to vacuolic structures in ischemic neurons. Increasing evidence suggests that the effects of autophagy are highly contextual. An insufficient autophagic response might render cells more susceptible to stress conditions whereas on the other hand prolonged overactivation of autophagy can lead to a complete self digestion of the cell. The extent of autophagy may represent a master switch between cell survival and cell death, and it will be of fundamental importance to dissect whether autophagy is primarily a strategy for survival or whether autophagy can also be a part of a cell death program and thus contribute to cell death after cerebral ischemia. A profound understanding of the biological effects and the mechanisms underlying ischemia-induced autophagy in neurons might be helpful in seeking effective new treatments for cerebral ischemia.

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“…Both cell bodies and dendrites are immunoreactive. Procaspase-3 in dendrites and synaptic terminals plays an important role in the local activation of the apoptotic cascade, spreading from the dendrite to the cell body, which has been impressively documented in postischemic brain lesion [38] . Also regulating synaptic plasticity, reversible activation of the apoptotic cascade can occur in synapses during physiological activation of glutamate receptors [38] .…”

Section: Discussionmentioning

confidence: 99%

Caspase-3 Immunoreactivity in Different Cortical Areas of Young and Aging Macaque <i>(Macaca</i><i>mulatta) </i>Monkeys

Zhang

Lorke

et al. 2006

Neurosignals

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It has been shown that cytochrome-c-dependent caspase-3 activation is significantly elevated in the aging macaque brain. To assess the underlying age-related changes in the cellular distribution of caspase-3, we have examined the motor cortex, cerebellum and hippocampus of young (4-year-old, n = 4) and old (20-year-old, n = 4)rhesus monkeys by immunohistochemistry. Western blot analyses of brain homogenate showed that the antibody reacted only with inactive 32-kDa procaspase and its active 20- and 17-kDa subunits, formed after granzyme B exposure. In the motor cortex, pyramidal cells of layers III and V were moderately labeled; the underlying white matter contained weakly stained astrocytes. In the hippocampus, hilar neurons and pyramidal cells in CA3 showed the strongest immunoreaction, pyramidal cells in CA1 and granule cells of the dentate gyrus were also strongly labeled. In contrast, CA2 pyramidal cells were only weakly stained, and neurons of the molecular layer were unlabeled. Weak caspase-3 immunoreaction of CA2 neurons parallels known decreased susceptibility to apoptosis. In the cerebellar cortex, clusters of strongly labeled Purkinje cells were observed next to groups of weakly and unstained cells; granule cells were generally unstained. The brains of aging monkeys displayed a similar pattern of caspase-3 immunoreactivity. In neocortical layer V, however, scattered very strongly labeled pyramidal cells were regularly detected, which were not observed in younger animals. This clustering of caspase-3 indicates increased vulnerability of a subset of pyramidal cells in the aging brain.

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Post-ischemic activation of caspase-3 in the rat hippocampus: evidence of an axonal and dendritic localisation

Cited by 39 publications

References 47 publications

Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection

Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection

Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of the same coin?

Caspase-3 Immunoreactivity in Different Cortical Areas of Young and Aging Macaque <i>(Macaca</i><i>mulatta) </i>Monkeys

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