Copper and zinc as modulators of neuronal excitability in a physiologically significant concentration range

Aedo, Felipe; Delgado, Ricardo; Wolff, Daniel; Vergara, Cecilia

doi:10.1016/j.neuint.2006.12.001

Cited by 28 publications

(19 citation statements)

References 45 publications

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“…[61] These results, which mirror others observed with much higher concentrations of Zn 2+ , have been attributed to differential occupancy of high and low affinity binding sites within sodium channels. [61] Ultimately, the physiological relevance of these observations depends on the presence of sufficient inhibitory concentrations of synaptic Cu 2+ , estimates of which span several orders of magnitude. [59] …”

Section: How Does a Redox Active Metal Control Neurochemical Signasupporting

confidence: 71%

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’

Goldberg

Loas

Lippard

2016

Israel Journal of Chemistry

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Metal ions perform critical and diverse functions in nervous system physiology and pathology. The field of metalloneurochemistry aims to understand the mechanistic bases for these varied roles at the molecular level. Here, we review several areas of research that illustrate progress toward achieving this ambitious goal and identify key challenges for the future. We examine the use of lithium as a mood stabilizer, the roles of mobile zinc and copper in the synapse, the interplay of nitric oxide and metals in retrograde signaling, and the regulation of iron homeostasis in the brain. These topics were chosen to demonstrate not only the breadth of the field, but also to highlight opportunities for discovery by studying such complex systems in greater detail. We are beginning to uncover the principles by which receptors and transmitters utilize metal ions to modulate neurotransmission. These advances have revealed exciting new insights into the intricate mechanisms that give rise to learning, memory, and sensory perception, while opening many new avenues for further exploration.

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Section: How Does a Redox Active Metal Control Neurochemical Signasupporting

confidence: 71%

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’

Goldberg

Loas

Lippard

2016

Israel Journal of Chemistry

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“…Inhibition of olfaction by metals such as copper can underlie neurobehavioral injury (Sandahl et al 2007). Copper is also known to have neuronal excitability potential (Aedo et al 2007) and it was interesting that we observed excitatory responses (e.g. jumping behaviors and rapid bursts of swimming) in a number of fish exposed to 40 ppb Cu.…”

Section: Discussionmentioning

confidence: 90%

Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures

Tilton

Bammler

Gallagher

2011

Comparative Biochemistry and Physiology Part C: Toxicology &

103

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Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair swimming behavior in fish. However, the impact to swimming behavior from exposure to mixtures of neurotoxicants has received little attention. In the current study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to investigate in vivo mixture interactions involving two chemical classes. Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 μM, 0.25 μM, 0.6 μM, or 6.3, 16, 40 ppb), chlorpyrifos (CPF, 0.1 μM, 0.25 μM, 0.6 μM, or 35, 88, 220 ppb) and binary mixtures for 24 hr to better understand the effects of Cu on CPF neurotoxicity. Exposure to CPF increased the number of animals undergoing freeze responses (an anti-predator behavior) and, at the highest CPF dose (0.6 μM), elicited a decrease in zebrafish swimming rates. Interestingly, the addition of Cu caused a reduction in the number of zebrafish in the CPF-exposure groups undergoing freeze responses. There was no evidence of additive or synergistic toxicity between Cu and CPF. Although muscle AChE activity was significantly reduced by CPF, there was a relatively poor relationship among muscle AChE concentrations and swimming behavior, suggesting non-muscle AChE mechanisms in the loss of swimming behavior. In summary, we have observed a modulating effect of Cu on CPF swimming impairment that appears to involve both AChE and non-AChE mechanisms. Our study supports the utility of zebrafish in understanding chemical mixture interactions and neurobehavioral injury.

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“…These characteristics are quite similar to Zn. The released Cu reportedly influences various receptors, including N-methyl-D-aspartate (NMDA)-type glutamate receptor, AMPA-type glutamate receptor and GABA receptor to modulate the neuronal activity [16].…”

Section: Cu and Normal Prion Proteinmentioning

confidence: 99%

Disruption of Metal Homeostasis and the Pathogenesis of Prion Diseases

Kawahara¹,

Tanaka²,

Mizuno³

2017

Prion - An Overview

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Prion diseases are progressive neurodegenerative diseases that are associated with the conformational conversion of normal cellular prion protein (PrP C ) into abnormal pathogenic prion protein (PrP Sc ). PrP C is a metal-binding protein that is located in the synapse and possesses the ability to bind to various metals, including Cu, Zn, Mn and Fe. Moreover, increasing evidence suggests that PrP C plays essential roles in the maintenance of metal homeostasis in the synapse. Trace elements have a crucial influence on the conformational change of PrP C . Given that other disease-related proteins such as β-amyloid protein and its precursor protein (APP) in Alzheimer's disease also exist in the synapse and possess a metal-binding ability, an interaction between PrP and metals and between PrP and APP, may occur in the synapse; the resulting metal homeostasis may lead to the pathogenesis of prion diseases. Here, we review our studies and other new findings that inform the current understanding of the link between trace elements and physiological functions of PrP C and the neurotoxicity of PrP Sc .

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Copper and zinc as modulators of neuronal excitability in a physiologically significant concentration range

Cited by 28 publications

References 45 publications

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’

Metalloneurochemistry and the Pierian Spring: ‘Shallow Draughts Intoxicate the Brain’

Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures

Disruption of Metal Homeostasis and the Pathogenesis of Prion Diseases

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