Intranasal exposure to uranium results in direct transfer to the brain along olfactory nerve bundles

Ibanez, Chrystelle; Suhard, David; Tessier, Christine; Delissen, Olivia; Lestaevel, Philippe; Dublineau, Isabelle; Gourmelon, P.

doi:10.1111/nan.12061

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…Instillation avoids deposition in the lungs and/or on the fur which can occur with nose-only or whole-body inhalation exposure. Instillation has been used in several other studies to demonstrate the translocation of soluble or particulate materials in rodents (Evans and Hastings, 1992;Gianutsos et al, 1997;Henriksson et al, 1997;Ibanez et al, 2014;Tjälve et al, 1996). A lack of sensitivity of the animal model used in the present study (intranasal instillations in the rat) to explain the negative results obtained with alumina, is unlikely.…”

Section: Discussionmentioning

confidence: 99%

Study of potential transfer of aluminum to the brain via the olfactory pathway

et al. 2018

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Many employees in the aluminum industry are exposed to a range of aluminum compounds by inhalation, and the presence of ultrafine particles in the workplace has become a concern to occupational health professionals. Some metal salts and metal oxides have been shown to enter the brain through the olfactory route, bypassing the blood-brain barrier, but few studies have examined whether aluminum compounds also use this pathway. In this context, we sought to determine whether aluminum was found in rat olfactory bulbs and whether its transfer depended on physicochemical characteristics such as solubility and granulometry. Aluminum salts (chloride and fluoride) and various nanometric aluminum oxides (13nm, 20nm and 40-50nm) were administered to rats by intranasal instillation through one nostril (10μg Al/30μL for 10days). Olfactory bulbs (ipsilateral and contralateral relative to instilled nostril) were harvested and the aluminum content was determined by graphite furnace atomic absorption spectrometry after tissue mineralization. Some transfer of aluminum salts to the central nervous system via the olfactory route was observed, with the more soluble aluminum chloride being transferred at higher levels than aluminum fluoride. No cerebral translocation of any of the aluminas studied was detected.

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Section: Discussionmentioning

confidence: 99%

Study of potential transfer of aluminum to the brain via the olfactory pathway

et al. 2018

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“…In addition to the neuronal pathway, nanoparticles could gain access to the CNS through the extracellular pathways (perineuronal, perivascular and cerebrospinal fluid pathways). As an example, to comfort initial inhalation studies using uranium aerosol (Tournier et al, 2009) in rats, that suggested the existence of an olfactory transport, a second wave of experiments using instillation of soluble uranium in the nasal cavity was performed (Ibanez et al, 2014).…”

Section: Extracellular Pathways Excluding Bloodmentioning

confidence: 99%

Nano- and neurotoxicology: An emerging discipline

Bencsik

Lestaevel

Canu

2018

Progress in Neurobiology

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The present critical review analyzes the question of how nanoparticles from continuously growing industrial production and use of nanomaterials may impact human brain health. Available evidence suggests incomplete effectiveness of protective barriers of the brain against nanoparticles translocation to the brain. This raises concerns of potential effects of manufactured nanoparticles on brain functions, given that nanoparticle's potential to induce oxidative stress, inflammation, death by apoptosis, or changes in the level of expression of certain neurotransmitters. Most concerns have not been studied sufficiently and many questions are still open: Are the findings in animals transposable to humans? What happens when exposure is chronic or protracted? What happens to the developing brain when exposure occurs in utero? Are some nanoparticles more deleterious, given their ability to alter protein conformations and aggregation? Aside from developments in nanomedicine, the evidence already available fully justifies the need to specifically evaluate the interactions between nanoparticles and the nervous system. The available data clearly indicates the need for original dedicated experimental models and tools for neurotoxicological research on the one hand, and the need for epidemiological studies of neurodegenerative diseases in manufactured nanoparticle-exposed populations, on the other. A combination of nanotoxicology with neurology in a novel discipline, with its specific tools and methods of investigation, should enable answering still unresolved questions.

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“…Mechanisms for adaptation to humans seem to have occurred in the BP precursor, B. pseudopertussis , at an earlier time, taking place for BP by gene loss (Diavatopoulos et al, 2005 ). B. pertussis infection damages nasal ciliated epithelium, a structure which transfers uranium to brain along olfactory nerve bundles (Wilson et al, 1991 ; Ibáñez et al, 2014 ).…”

Section: Data Supporting Amyloid-related Etiology According To Specifmentioning

confidence: 99%

Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features

Pedro‐Cuesta

Martinez‐Martín

Rábano

et al. 2016

Front. Aging Neurosci.

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Background: During the last two decades, protein aggregation at all organismal levels, from viruses to humans, has emerged from a neglected area of protein science to become a central issue in biology and biomedicine. This article constitutes a risk-based review aimed at supporting an etiologic scenario of selected, sporadic, protein-associated, i.e., conformational, neurodegenerative disorders (NDDs), and their vascular- and metabolic-associated ailments.Methods: A rationale is adopted, to incorporate selected clinical data and results from animal-model research, complementing epidemiologic evidences reported in two prior articles.Findings: Theory is formulated assuming an underlying conformational transmission mechanism, mediated either by horizontal transfer of mammalian genes coding for specific aggregation-prone proteins, or by xeno-templating between bacterial and host proteins. We build a few population-based and experimentally-testable hypotheses focusing on: (1) non-disposable surgical instruments for sporadic Creutzfeldt-Jakob disease (sCJD) and other rapid progressive neurodegenerative dementia (sRPNDd), multiple system atrophy (MSA), and motor neuron disease (MND); and (2) specific bacterial infections such as B. pertussis and E. coli for all forms, but particularly for late-life sporadic conformational, NDDs, type 2 diabetes mellitus (T2DM), and atherosclerosis where natural protein fibrils present in such organisms as a result of adaptation to the human host induce prion-like mechanisms.Conclusion: Implications for cohort alignment and experimental animal research are discussed and research lines proposed.

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Intranasal exposure to uranium results in direct transfer to the brain along olfactory nerve bundles

Cited by 23 publications

References 32 publications

Study of potential transfer of aluminum to the brain via the olfactory pathway

Study of potential transfer of aluminum to the brain via the olfactory pathway

Nano- and neurotoxicology: An emerging discipline

Etiologic Framework for the Study of Neurodegenerative Disorders as Well as Vascular and Metabolic Comorbidities on the Grounds of Shared Epidemiologic and Biologic Features

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