The aging neurogenic subventricular zone

Luo, Jie; Daniels, Stephen B.; Lennington, Jessica B.; Notti, Ryan Q.; Conover, Joanne C.

doi:10.1111/j.1474-9726.2006.00197.x

Cited by 259 publications

(302 citation statements)

References 51 publications

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“…We and others have reported previously that between ~3 to ~24 months of age, the number of BrdU-labeled cells decreases by ~90% in DG and by ~50% in SVZ [19,23]. In the present study, the number of cleaved caspase-3-immunopositive cells decreased by ~75% in DG and by ~50% in SVZ (Fig.…”

Section: Resultssupporting

confidence: 72%

“…We and others have reported a gradual decline of neurogenesis with normal aging in rats and mice [8,19,23], which could be due to either decreased NPC neuroproliferation or increased NPC death.…”

Section: Discussionmentioning

confidence: 68%

“…Although NPC proliferation in the DG and SVZ is reduced with aging [17,19,23], how programmed cell death of NPCs may be altered during normal brain aging is unknown. Therefore, we investigated the expression of caspase activation products in neuroproliferative zones of the young, young-adult, middle-aged and aged rat brain, as well as the effect of caspase inhibition on neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

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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: Resultssupporting

confidence: 72%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

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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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“…It is not clear if newborn neurons replace old interneurons or if they are added and preexisting interneurons are maintained. Because subventricular zone stem cell proliferation decreases with age (30,36,37), we hypothesized that the total number of granule cells would decrease proportionately. Here, we provide evidence that granule cells (total and deep populations) are stable during aging.…”

Section: Discussionmentioning

confidence: 99%

Age-induced disruption of selective olfactory bulb synaptic circuits

Richard

Taylor²,

Greer³

2010

Proc. Natl. Acad. Sci. U.S.A.

127

125

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Little is known about how normal aging affects the brain. Recent evidence suggests that neuronal loss is not ubiquitous in aging neocortex. Instead, subtle and still controversial, region-and layerspecific alterations of neuron morphology and synapses are reported during aging, leading to the notion that discrete changes in neural circuitry may underlie age-related cognitive deficits. Although deficits in sensory function suggest that primary sensory cortices are affected by aging, our understanding of the age-related cellular and molecular changes is sparse. To assess the effect of aging on the organization of olfactory bulb (OB) circuitry, we carried out quantitative morphometric analyses in the mouse OB at 2, 6, 12, 18, and 24 mo. Our data establish that the volumes of the major OB layers do not change during aging. Parallel to this, we are unique in demonstrating that the stereotypic glomerular convergence of M72-GFP OSN axons in the OB is preserved during aging. We then provide unique evidence of the stability of projection neurons and interneurons subpopulations in the aging mouse OB, arguing against the notion of an age-dependent widespread loss of neurons. Finally, we show ultrastructurally a significant layer-specific loss of synapses; synaptic density is reduced in the glomerular layer but not the external plexiform layer, leading to an imbalance in OB circuitry. These results suggest that reduction of afferent synaptic input and local modulatory circuit synapses in OB glomeruli may contribute to specific age-related alterations of the olfactory function.aging | axodendritic synapses | dendrodendritic synapses | mitral cells A ge-related neurodegenerative diseases, such as Parkinson and Alzheimer's, involve localized or widespread neuronal loss, but little is known about the changes occurring in the brain during normal aging. A growing consensus argues against widespread neuronal loss and atrophy during aging (1, 2). Rather, subtle region-and layer-specific alterations of neuronal morphology and synaptic connections are reported in the neocortex and hippocampus, where they may contribute to age-related cognitive deficits.The laminar organization of olfactory bulb (OB) neurons and synapses provides a simplified cortical model in which we can probe principles of neuronal and synaptic organization during aging. Sensory functions are affected by aging, including alterations in olfactory acuity, discrimination, and memory (3-12). The OB is the first central relay in the pathway processing odor information: it receives afferent input from olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) and is responsible for detecting odors in the nasal cavity. OSN axons synapse on mitral/tufted cell dendrites in OB glomerular neuropils. OB local interneurons modulate the activity of mitral/tufted cells, contributing to odor signal integration, before propagation to the piriform cortex. Projections from the OE to the OB are organized in an odor receptor (OR) map; each subpopulation of OSNs expressin...

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“…Aging is associated with reduced neurogenesis in the mouse SVZ and SGZ (Encinas et al., 2011; Enwere et al., 2004; Lugert et al., 2010; Luo, Daniels, Lennington, Notti & Conover, 2006), which might lead to decreased olfactory function and cognitive hippocampus‐dependent impairment (Goncalves et al., 2016; Lledo & Valley, 2016). This age‐associated neurogenic decline appears to be caused both by a depletion in the NSPC pool of the aged niche (Ahlenius, Visan, Kokaia, Lindvall & Kokaia, 2009; Bouab, Paliouras, Aumont, Forest‐Berard & Fernandes, 2011; Corenblum et al., 2016; Enwere et al., 2004; Luo et al., 2006; Maslov, Barone, Plunkett & Pruitt, 2004; Molofsky et al., 2006; Stoll et al., 2011) and by the decreased capacity of the remaining NSPCs to sustain proliferation and neuronal differentiation, as revealed by in vitro studies (Ahlenius et al., 2009; Apostolopoulou et al., 2017; Corenblum et al., 2016; Daynac, Morizur, Chicheportiche, Mouthon & Boussin, 2016; Daynac et al., 2014; L'Episcopo et al., 2013; Shi et al., 2017; Zhu et al., 2014). NSPCs undergo cell autonomous age‐related changes that affect intracellular molecular pathways, including the altered expression of telomerase and cell cycle regulators, which have been linked to the decline in NSPC proliferation upon aging (Caporaso, Lim, Alvarez‐Buylla & Chao, 2003; Molofsky et al., 2006; Nishino, Kim, Chada & Morrison, 2008).…”

Section: Introductionmentioning

confidence: 99%

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

et al. 2018

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SummaryAdult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age‐associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ‐derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age‐dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age‐related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age‐associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age‐related neurogenic decline.

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The aging neurogenic subventricular zone

Cited by 259 publications

References 51 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

Age-induced disruption of selective olfactory bulb synaptic circuits

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age‐associated neurogenic decline

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