Altered epithelial density and expansion of bulbar projections of a discrete HSP70 immunoreactive subpopulation of rat olfactory receptor neurons in reconstituting olfactory epithelium following exposure to methyl bromide

Carr, Virginia McMillan; Ring, George; Youngentob, Steven L.; Schwob, James E.; Farbman, Albert I.

doi:10.1002/cne.11020

Cited by 20 publications

(11 citation statements)

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“…Finally, we found that OSNs were able to at least partially reestablish functional connections to the OB even after lesions severe enough to permit only minor recovery of the OSN population. These results expand on earlier anatomical studies that have reported regeneration and glomerular convergence of a few OR- and histologically-defined OSN populations (Schwob et al, 1999; Costanzo, 2000; St. John and Key, 2003; McMillan Carr et al, 2004; Blanco-Hernández et al, 2012) and are consistent with a recent report that discriminative odor memories are preserved after OSN lesion and recovery (Blanco-Hernández et al, 2012). …”

Section: Discussionsupporting

confidence: 91%

“…This result does not simply reflect the reconstitution of normal zones of odorant receptor (OR) expression in the OE and the maintenance of rhinotopic projections from the OE to OB (Schoenfeld et al, 1994; Cummings et al, 2000; Iwema et al, 2004), as OSNs projecting to OB domains are interspersed in the OE (Bozza et al, 2009). The reconstitution of functional topography after OSN regeneration is consistent with earlier anatomical studies examining the targeting of P2- or M72-expressing OSNs or of immunohistochemically-defined OSN subsets (Cummings et al, 2000; St. John and Key, 2003; McMillan Carr et al, 2004; Blanco-Hernández et al, 2012); these studies found that OSNs project to glomeruli in topographically similar locations as in control animals, although with clear errors in targeting. The fact that, in this study, spH response maps—even those involving many glomeruli—retain a spatial organization that matches that before lesion suggests that regenerated OSN axons do not randomly converge onto OB glomeruli but instead preferentially target their appropriate domain on the OB surface.…”

Section: Discussionsupporting

confidence: 86%

“…Previous studies have demonstrated that, in the adult, the targeting of OSN axons to glomeruli after lesion is subject to errors that do not occur during development (Schwob et al, 1999; Costanzo, 2000; St. John and Key, 2003; McMillan Carr et al, 2004; Blanco-Hernández et al, 2012). These errors include a lack of exclusive convergence of OSNs onto the same glomerulus and projection of at least some axons of a given OSN population to multiple, dispersed glomeruli (Costanzo, 2000; St. John and Key, 2003; Blanco-Hernández et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

Cheung¹,

Jang²,

Schwob³

et al. 2014

Front. Neural Circuits

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The olfactory system has a unique capacity for recovery from peripheral damage. After injury to the olfactory epithelium (OE), olfactory sensory neurons (OSNs) regenerate and re-converge on target glomeruli of the olfactory bulb (OB). Thus far, this process has been described anatomically for only a few defined populations of OSNs. Here we characterize this regeneration at a functional level by assessing how odor representations carried by OSN inputs to the OB recover after massive loss and regeneration of the sensory neuron population. We used chronic imaging of mice expressing synaptopHluorin in OSNs to monitor odor representations in the dorsal OB before lesion by the olfactotoxin methyl bromide and after a 12 week recovery period. Methyl bromide eliminated functional inputs to the OB, and these inputs recovered to near-normal levels of response magnitude within 12 weeks. We also found that the functional topography of odor representations recovered after lesion, with odorants evoking OSN input to glomerular foci within the same functional domains as before lesion. At a finer spatial scale, however, we found evidence for mistargeting of regenerated OSN axons onto OB targets, with odorants evoking synaptopHluorin signals in small foci that did not conform to a typical glomerular structure but whose distribution was nonetheless odorant-specific. These results indicate that OSNs have a robust ability to reestablish functional inputs to the OB and that the mechanisms underlying the topography of bulbar reinnervation during development persist in the adult and allow primary sensory representations to be largely restored after massive sensory neuron loss.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

Cheung¹,

Jang²,

Schwob³

et al. 2014

Front. Neural Circuits

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“…These stages have been termed proliferating neuronal precursor cells → immature neurons → mature neurons (Calof et al,1998; Mackay‐Sim and Chuah,2000; Newman et al,2000). Furthermore, perturbation paradigms of the olfactory system, such as chemical injuries to the OE (Herzog and Otto,1999) and olfactory bulbectomy (Margolis et al,1991; Biffo et al,1992; Carr and Farbman,1992), in conjunction with lineage analysis employing replication incompetent retroviruses (MacDonald et al,1996; Goldstein et al,1997), have characterized the progression of neurogenesis with respect to the cell types and at least some of the molecules likely to be involved (Schwob,2002; McMillan Carr et al,2004; Youngentob et al,2004).…”

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confidence: 99%

In vivo and in vitro neurogenesis in human olfactory epithelium

et al. 2005

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The birth and differentiation of neurons have been extensively studied in the olfactory epithelium (OE) of rodents but not in humans. The goal of this study was to characterize cellular composition and molecular expression of human OE in vivo and in vitro. In rodent OE, there are horizontal basal cells and globose basal cells that are morphologically and functionally distinct. In human OE, however, there appears to be no morphological distinction among basal cells, with almost all cells having round cell bodies similar to rodent globose basal cells. Unlike the case in rodents, human basal cells, including putative neuronal precursors, express p75NGFR, suggesting a distinctive role for p75NGFR in human OE neurogenesis. Molecular expression of neuronal cells during differentiation in human OE grossly follows that in rodents. However, the topographical organization of immature and mature ORNs in human OE differs from that of rodents, in that immature and mature ORNs in humans are dispersed throughout the OE, whereas rodent counterparts have a highly laminar organization. These observations together suggest that the birth and differentiation of neuronal cells in human OE differ from those in rodents. In OE explant culture, neuronal cells derived from human OE biopsy express markers for immature and mature neurons, grossly recapitulating neuronal differentiation of olfactory neurons in vivo. Furthermore, small numbers of cells are doubly label for bromodeoxyuridine and olfactory marker protein, indicating that neuronal cells born in vitro reach maturity. These data highlight species-related differences in OE development and demonstrate the utility of explant culture for experimental studies of human neuronal development.

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“…Additionally, recent data provide evidence for the mechanistic aspects of methyl bromide neurotoxicity and point to its ability to alter epithelial density and expansion of bulbar projections [64], to inhibit creatine kinase in rat brain [65] or its effects on matrix metalloproteinase-9 and -2 in the olfactory bulb following methyl bromide gas exposure [66]. …”

Section: Resultsmentioning

confidence: 99%

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

Budnik¹,

Kloth²,

Velasco-Garrido

et al. 2012

Environ Health

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BackgroundAlthough ozone-depleting methyl bromide was destined for phase-out by 2005, it is still widely applied as a consequence of various critical-use-exemptions and mandatory international regulations aiming to restrict the spread of pests and alien species (e.g. in globalized transport and storage). The withdrawal of methyl bromide because of its environmental risk could fortuitously help in the containment of its human toxicity.MethodsWe performed a systematic review of the literature, including in vitro toxicological and epidemiological studies of occupational and community exposure to the halogenated hydrocarbon pesticide methyl bromide. We focused on toxic (especially chronic) or carcinogenic effects from the use of methyl bromide, on biomonitoring data and reference values. Eligible epidemiological studies were subjected to meta-analysis.ResultsOut of the 542 peer reviewed publications between 1990-2011, we found only 91 referring to toxicity of methyl bromide and 29 using the term "carcinogenic", "neoplastic" or "mutagenic". Several studies provide new additional data pertaining to the mechanistic aspects of methyl bromide toxicity. Few studies have performed a detailed exposure assessment including biomonitoring. Three evaluated epidemiological studies assessed a possible association between cancer and methyl bromide. Overall, exposure to methyl bromide is associated with an increased risk of prostate cancer OR, 1.21; 95% CI (0,98-1.49), P = 0.076. Two epidemiological studies have analyzed environmental, non-occupational exposure to methyl bromide providing evidence for its health risk to the general public. None of the epidemiological studies addressed its use as a fumigant in freight containers, although recent field and case reports do refer to its toxic effects associated with its use in shipping and storage.ConclusionsBoth the epidemiological evidence and toxicological data suggest a possible link between methyl bromide exposure and serious health problems, including prostate cancer risk from occupational and community exposure. The environmental risks of methyl bromide are not in doubt, but also its health risks, especially for genetically predisposed subjects, should not be underestimated.

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Altered epithelial density and expansion of bulbar projections of a discrete HSP70 immunoreactive subpopulation of rat olfactory receptor neurons in reconstituting olfactory epithelium following exposure to methyl bromide

Cited by 20 publications

References 80 publications

Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb

In vivo and in vitro neurogenesis in human olfactory epithelium

Prostate cancer and toxicity from critical use exemptions of methyl bromide: Environmental protection helps protect against human health risks

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