Programmed Cell Death of Adult-Generated Hippocampal Neurons Is Mediated by the Proapoptotic Gene Bax

Sun, Woong; Winseck, Adam K.; Vinsant, Sharon; Park, Ok Hee; Kim, H.; Oppenheim, Ronald W.

doi:10.1523/jneurosci.1436-04.2004

Cited by 179 publications

(214 citation statements)

References 59 publications

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“…Our results show that caspase-3 activation may also be important for programmed death of NPCs in the adult SGZ and SVZ in vivo. Consistent with this idea, programmed cell death in the adult hippocampus is dramatically reduced in Bax-knockout mice [27] and after caspase inhibition in rats. Caspase-8 and -9 are upstream initiators of caspase-3-mediated death in what is considered 'classical' apoptosis [26].…”

Section: Discussionmentioning

confidence: 52%

Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia

Tang

Wang

Xie

et al. 2009

Neurobiology of Aging

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The observed age-related decline in neurogenesis may result from reduced proliferation or increased death rate of neuronal precursor cells (NPCs). We found that caspase-3, but not caspase-6, -7, or -9, was activated in NPCs in neurogenic regions of young, young-adult, middle-aged and aged rat brains. The number of capase-3-immunoreactive cells was highest in young and lowest in aged rats. Surprisingly, intraventricular administration of a caspase-3 inhibitor failed to restore the number of BrdU-positive cells in the aged dentate gyrus, suggesting that the age-related decline in neurogenesis may be attributable primarily to reduced proliferation. Additionally, we also found that NPCs in the subventricular zone of young-adult and aged rat brain were increased after focal cerebral ischemia, suggesting that the increase in neurogenesis induced by ischemia may result from an increase in the rate of NPC proliferation, but not from a decrease in NPC death. Thus, our results suggest that agerelated and injury-induced changes in the rate of neurogenesis are controlled at the level of NPC proliferation. Furthermore, our results may imply that the mechanisms that maintain a stable population of NPCs in the normal adult and in the ischemic brain, which account for the observed age-dependent reduction or injury-induced increases in neurogenesis, impinge on the regulation of cell division at the NPC level.

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Section: Discussionmentioning

confidence: 52%

Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia

Tang

Wang

Xie

et al. 2009

Neurobiology of Aging

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“…However, the rescued neurons in the VCG of the ND -/-Bax -/-mice failed to migrate properly, indicating that NeuroD is required for the migration of these neurons. Bax is required for neuronal death in the developing brain (Deckwerth et al, 1996) and in adult neural stem cells (Sun et al, 2004). However, the neural development of the Bax -/-mice was largely normal, except that there were fewer apoptotic neurons in the developing CNS (White et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

NeuroD Regulates Neuronal Migration

Kim

2013

Molecules and Cells

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NeuroD is required for the survival of many subtypes of developing neurons in the vertebrate central nervous system. Because NeuroD-deficient neurons in the hippocampus, cerebellum, and inner ear die prematurely in the early stage of neurogenesis, the role of NeuroD during the later stages of neurogenesis of these cell subtypes is not well understood. In addition, the mechanism of NeuroDdeficient neuronal death has not been investigated. It was hypothesized that NeuroD-dependent neuronal death occurs through a Bax-dependent apoptotic pathway. Based on this hypothesis, this study attempted to rescue neuronal cell death by deleting the Bax gene in NeuroD null mice to investigate the role of NeuroD in surviving neurons. The NeuroD and Bax double null mice displayed a decrease in the number of apoptotic cells in the hippocampus and the cerebellum and the rescue of vestibulocochlear ganglion (VCG) neurons that failed to migrate and innervate. In addition, at E13.5, the NeuroD -/-Bax -/-VCG neurons failed to express TrkB and TrkC, which are known to be essential for the survival of those neurons. These data suggest that neuronal death in NeuroD null mice is mediated by Bax-dependent apoptosis and that NeuroD is required for the migration of VCG neurons. Finally, these data show that TrkB and TrkC expression in E13.5 VCG neurons requires NeuroD and that TrkB and TrkC expression may be necessary for the normal migration and innervations of those neurons.

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“…Excess amounts of proapoptotic Bax in its active form can also directly induce cytochrome c release, resulting in formation of the apoptosome complex composed of Apaf-1, caspase-9, and ATP, triggering cell death (Korhonen et al, 2003;Roucou and Martinou, 2001). From studies using Bax null mutant mice, it has recently been shown that in the adult hippocampus, programmed cell death as well as proliferation, migration, and maturation of adult-generated DG neurons is mainly dependent on Bax (Sun et al, 2004). On the other hand, the neuroprotective effects of fluoxetine in the hippocampus are only recently coming to light.…”

Section: Discussionmentioning

confidence: 99%

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

Kosten

Galloway

Duman

et al. 2007

Neuropsychopharmacol

148

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Apoptosis has been proposed as a contributing cellular mechanism to the structural alterations that have been observed in stress-related mood disorders. Antidepressants, on the other hand, are hypothesized to exert trophic and/or neuroprotective actions. The present study examined the regulation of the major antiapoptotic (Bcl-2, Bcl-xl) and proapoptotic (Bax) genes by repeated unpredictable stress (an animal model of depression) and antidepressant treatments (ADT). In adult rats, exposure to unpredictable stress reduced Bcl-2 mRNA levels in the central nucleus of the amygdala (CeA), cingulate (Cg), and frontal (Fr) cortices. Bcl-xl mRNA was significantly decreased in hippocampal subfields. In contrast, chronic administration of clinically effective antidepressants from four different classes, ie fluoxetine, reboxetine, tranylcypromine, and electroconvulsive seizures (ECS) upregulated Bcl-2 mRNA expression in the Cg, Fr, and CeA. Reboxetine, tranylcypromine, and ECS selectively increased Bcl-xl, but not Bcl-2 mRNA expression in the hippocampus. Chemical ADT but not ECS, robustly enhanced Bcl-2 expression in the medial amygdaloid nucleus and ventromedial hypothalamus. Fluoxetine did not influence Bcl-xl expression in the hippocampus, but it was the only ADT that decreased Bax expression in this region. In the CeA, again in direct contrast to the stress effects, exposure to all classes of ADTs significantly increased Bcl-2 mRNA. The selective regulation of Bcl-xl and Bax in hippocampal subfields and of Bcl-2 in the Cg cortex, amygdala, and hypothalamus suggests that these cellular adaptations contribute to the long-term neural plastic adaptations to stress and ADTs in cortical, hypothalamic, and limbic brain structures.

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Programmed Cell Death of Adult-Generated Hippocampal Neurons Is Mediated by the Proapoptotic Gene Bax

Cited by 179 publications

References 59 publications

Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia

Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia

NeuroD Regulates Neuronal Migration

Repeated Unpredictable Stress and Antidepressants Differentially Regulate Expression of the Bcl-2 Family of Apoptotic Genes in Rat Cortical, Hippocampal, and Limbic Brain Structures

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