Additive Impairment of Synaptic Signaling in Cultured Cortical Neurons by Exogenously-Applied Oligomerized Amyloid-β and Airborne Nanoparticles Generated during Photocopying

Lee, Sang-Mook; Sohal, Ikjot Singh; Therrien, Mikaela; Pal, Anoop K.; Bello, Dhimiter; Shea, Thomas B.

doi:10.3233/jad-150099

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…Since NP from TPE represent a complex mixture, containing a large organic component, a sizeable amount of metal oxides, and other more volatile organics absorbed onto surface of PM, the toxicological testing framework for these particles should be expanded to evaluate other organ systems and endpoints-including but not limited to those related to cardiovascular, neurological, and blood systems. For example, Lee et al (2015) demonstrated a concentration-dependent inhibition of synaptic signaling by photocopy center NP in mouse cultured cortical neurons over 0.1-50 μg/mL of administered concentrations (corresponding to delivered concentrations of 0.2-10 μg/mL at 24 hour after taking into account dispersion and dosimetry modeling), and a synergistic effect between amyloid beta and NP. Equally important is utilization of screening assays to understand the impact of variability in chemical composition on toxicity, synergistic effects between organics and metals, and biokinetics of such particles from real world exposures, studies yet to be conducted.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs

Pirela¹,

Martin

Bello

et al. 2017

Critical Reviews in Toxicology

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Toner formulations used by laser printers (LP) and photocopiers (PC), collectively called “toner-based printing equipment” (TPE), are nano-enabled products (NEP) because they contain several engineered nanomaterials (ENM) that improve toner performance. It has been shown that during consumer use (printing), these ENM are released in the air, together with other semi volatile organic nanoparticles, and newly formed gaseous co-pollutants such as volatile organic compounds (VOC). The aim of this review is to detail and analyze physico-chemical and morphological (PCM), as well as the toxicological properties of particulate matter (PM) emissions from TPE. The review covers evolution of science since the early 2000, when this printing technology first became a subject of public interest, as well as the lagging regulatory framework around it. Important studies that have significantly changed our understanding of these exposures are also highlighted. The review continues with a critical appraisal of the most up-to-date cellular, animal and human toxicological evidence on the potential adverse human health effects of PM emitted from TPE. We highlight several limitations of existing studies, including: (i) use of high and often unrealistic doses in vitro or in vivo; (ii) unrealistically high dose rates in intratracheal instillation studies; (iii) improper use of toners as surrogate for emitted nanoparticles; (iv) lack of or inadequate PCM characterization of exposures; and (v) lack of dosimetry considerations in in vitro studies. Presently, there is compelling evidence that the PM01 from TPE are biologically active and capable of inducing oxidative stress in vitro and in vivo, respiratory tract inflammation in vivo (in rats) and in humans, several endpoints of cellular injury in monocultures and co-cultures, including moderate epigenetic modifications in vitro. In humans, limited epidemiological studies report typically 2-3 times higher prevalence of chronic cough, wheezing, nasal blockage, excessive sputum production, breathing difficulties, and shortness of breath, in copier operators relative to controls. Such symptoms can be exacerbated during chronic exposures, and in individuals susceptible to inhaled pollutants. Thus respiratory, immunological, cardiovascular, and other disorders may be developed following such exposures; however, further toxicological and larger scale molecular epidemiological studies must be done to fully understand the mechanism of action of these TPE emitted nanoparticles. Major research gaps have also been identified. Among them, a methodical risk assessment based on “real world” exposures rather than on the toner particles alone needs to be performed to provide the much-needed data to establish regulatory guidelines protective of individuals exposed to TPE emissions at both the occupational and consumer level. Industry-wide molecular epidemiology as well as mechanistic animal and human studies are also urgently needed.

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Section: Resultsmentioning

confidence: 99%

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs

Pirela¹,

Martin

Bello

et al. 2017

Critical Reviews in Toxicology

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“…A different class of environmental factors includes air quality/airborne contaminants. Airborne carbon nanoparticles of the sort emitted by standard photocopiers impaired complex synaptic signaling in cortical cultures and furthermore imparted an additive impact to that of Aβ at concentrations at which neither agent perturbed signaling alone [ 56 ]. Comparison of the geographical distribution of individuals with dementia or MCI as reported by the National Alzheimer’s Coordinating Center with ambient air concentrations of ozone and fine particulate matter (PM) suggested that ozone but not PM was associated with more rapid cognitive decline [ 57 ].…”

Section: What Are Some Upstream Events Contributing To Ad?mentioning

confidence: 99%

While I Still Remember: 30 Years of Alzheimer’s Disease Research

Shea

2018

JAD

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Turns out I have been a major contributor to the Journal of Alzheimer’s Disease over its 20-year history. As such, I was invited to provide a review of my work over the years. What follows is a retrospective of how the Alzheimer-related research of a Ph.D. (i.e., not an M.D.) transitioned from basic to clinical, and moved from bench to bedside and back again.I have included some of the more humorous and poignant twists along the way that some older players may find familiar and I hope might inspire some younger players to hang in there.

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Robot-Embodied Neuronal Networks as an Interactive Model of Learning

Shultz

Lee²,

Guaraldi³

et al. 2017

TONEUJ

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Background and Objective:The reductionist approach of neuronal cell culture has been useful for analyses of synaptic signaling. Murine cortical neurons in culture spontaneously form an ex vivo network capable of transmitting complex signals, and have been useful for analyses of several fundamental aspects of neuronal development hitherto difficult to clarify in situ. However, these networks lack the ability to receive and respond to sensory input from the environment as do neurons in vivo. Establishment of these networks in culture chambers containing multi-electrode arrays allows recording of synaptic activity as well as stimulation.Method:This article describes the embodiment of ex vivo neuronal networks neurons in a closed-loop cybernetic system, consisting of digitized video signals as sensory input and a robot arm as motor output.Results:In this system, the neuronal network essentially functions as a simple central nervous system. This embodied network displays the ability to track a target in a naturalistic environment. These findings underscore that ex vivo neuronal networks can respond to sensory input and direct motor output.Conclusion:These analyses may contribute to optimization of neuronal-computer interfaces for perceptive and locomotive prosthetic applications. Ex vivo networks display critical alterations in signal patterns following treatment with subcytotoxic concentrations of amyloid-beta. Future studies including comparison of tracking accuracy of embodied networks prepared from mice harboring key mutations with those from normal mice, accompanied with exposure to Abeta and/or other neurotoxins, may provide a useful model system for monitoring subtle impairment of neuronal function as well as normal and abnormal development.

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Additive Impairment of Synaptic Signaling in Cultured Cortical Neurons by Exogenously-Applied Oligomerized Amyloid-β and Airborne Nanoparticles Generated during Photocopying

Cited by 4 publications

References 17 publications

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs

Nanoparticle exposures from nano-enabled toner-based printing equipment and human health: state of science and future research needs

While I Still Remember: 30 Years of Alzheimer’s Disease Research

Robot-Embodied Neuronal Networks as an Interactive Model of Learning

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