Comparative study of aging in the mouse olfactory bulb

Mirich, Jennifer M.; Williams, Nathaniel C.; Berlau, Daniel J.; Brunjes, Peter C.

doi:10.1002/cne.10426

Cited by 84 publications

(85 citation statements)

References 61 publications

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“…Our results are unique in providing evidence that NeuN + GABAergic and TH + dopaminergic PG cells, which both receive direct input from OSN axons (25), are maintained during aging. Together with our data, reports on calretinin + and dopaminergic PG cells (17,30) converge on a relative stability of PG subpopulations during aging.…”

Section: Discussionsupporting

confidence: 88%

“…Contrary to earlier reports of extensive volume and cell losses in the aging brain, our data suggest more subtle region-and layer-specific changes (1, 2). In the OB, there are reports of both strain-and species-dependent effects of aging (14)(15)(16)(17). Our results, which included more intermediate time points, establish that OB volume is stable from 2 mo onward in C57BL/6J mice.…”

Section: Discussionsupporting

confidence: 70%

“…Newborn granule cells continuously integrate into the adult OB and preferentially settle in the deeper part of the GCL (28,29). Because neurogenesis decreases with aging (17,30), the deep GCL seemed more likely to be affected. However, the density and total number of granule cells in the deep GCL were stable during aging, as was the volume of this region (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Some agerelated changes in the OE and OB were reported, mainly in rats (4,(14)(15)(16)(17)(18)(19)(20), but none document the kinetics of the defects. Here, we report quantitative morphometric analyses of the aging mouse OB at 2, 6, 12, 18, and 24 mo, focusing on changes in layer morphology, neuronal populations, synaptic circuitry, and OR map.…”

mentioning

confidence: 99%

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Age-induced disruption of selective olfactory bulb synaptic circuits

Richard

Taylor²,

Greer³

2010

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

121

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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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Age-induced disruption of selective olfactory bulb synaptic circuits

Richard

Taylor²,

Greer³

2010

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

121

125

View full text Add to dashboard Cite

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“…6B,D, 7B). Double staining of the OB for activated caspase-3 and DNA fragmentation showed that the number of TUNEL-positive, active-caspase-3-positive, and TUNEL-positive/active-caspase-3-positive cells decreased in the aged OB, consistent with a previous report (Mirich et al, 2002) (Fig. 7A).…”

Section: Sema7a Is a Direct Substrate Of Caspase-9supporting

confidence: 92%

Caspase-9 Activation Revealed by Semaphorin 7A Cleavage Is Independent of Apoptosis in the Aged Olfactory Bulb

Ohsawa¹,

Hamada²,

Asou³

et al. 2009

J. Neurosci.

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Caspases are essential in multicellular organisms for inducing cell death during normal development and in the immune system. However, caspases can also trigger the degenerative process under certain conditions such as pathophysiological conditions and aging. Here, we identified Semaphorin 7A (Sema7A) as a novel substrate for caspase-9 that can be used to monitor caspase-9 activity in mice, and found nonapoptotic caspase-9 activation in the aged olfactory bulb (OB). Immunostaining of the OB for the caspase-9-cleaved form of Sema7A revealed abundant caspase-9-activated cells in 2-year-old (aged) but not in 2-month-old (young) mice. In fact, various regions of the aged brain, including the OB, exhibited an increased level of caspase-9 activity. However, the number of dying cells in the aged OB was, intriguingly, much lower (Ͻ20%) than in the OB of young mice. Furthermore, we found that the lower number dying cells in the aged OB was accompanied by a decreased expression of procaspase-3. These results suggest a survival strategy for aged OB neurons, which can no longer regenerate, in which the central apoptotic machinery downstream of caspase-9 is inactivated.

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