Astroglia as Metal Depots: Molecular Mechanisms for Metal Accumulation, Storage and Release

Tiffany‐Castiglioni, Evelyn; Qian, Yongchang

doi:10.1016/s0161-813x(01)00050-x

Cited by 140 publications

(72 citation statements)

References 104 publications

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“…In marked contrast to our results, a number of studies report inhibitory effects of Pb on neurite initiation or outgrowth in hippocampal, mesencephalic, and retinal ganglion neurons over a broad range of concentrations, including those we employed (Cline et al, 1996;Kern and Audesirk, 1995;Schneider et al, 2003;Scortegagna et al, 1998). However, positive neuritogenic effects have been observed in mixed hippocampal cultures and neural tumors (Audesirk et al, 1991;Crumpton et al, 2001), where neuron-glial cell interactions may play a modulatory role (Tiffany-Castiglioni et al, 1989;Tiffany-Castiglioni and Qian, 2001;Lindahl et al, 1999). However, in the current studies the stimulation of neurite outgrowth by Pb occurs directly and not through glia, as previous characterization indicates that 85% of cells exhibited neuronal markers, MAP2 or Fig.…”

Section: Discussioncontrasting

confidence: 85%

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Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Davidovics¹,

DiCicco‐Bloom²

2005

J. Neurosci. Res.

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Lead (Pb) persists as an environmental toxicant despite aggressive environmental and occupational regulation. Neurotoxicological effects of acute Pb poisoning range from subtle cognitive deficits, to clumsiness and ataxia, to coma and seizures. In adult neurotoxicity, reductions of blood Pb levels are often associated with reversal of clinical signs. In children, however, the effects are more likely to endure, with even low levels of chronic Pb exposure correlating with decreasing IQ. These persistent effects likely result from neurodevelopmental insults, such as altered cell survival or maturation, although the mechanisms have not been fully defined. In the present study we define the effects of moderate-level Pb exposure on mammalian neurogenesis using a well-characterized cortical precursor model. Gestational day 14.5 rat cerebral cortical precursor cells were cultured in defined media and cell number, precursor proliferation, apoptosis, and neuritic process outgrowth were assessed following exposure to a range of Pb acetate concentrations. Surprisingly, whereas a concentration of 30 microg/ml Pb acetate was acutely toxic to neurons, concentrations between 1 and 10 microg/ml Pb acetate (approximately 3 microM and 30 microM Pb, respectively) increased cell number: 10 times as many cells exposed to 10 microg/ml Pb were present on day 4 as compared to control. The increase in cell number was not a result of increased proliferation, however, as DNA synthesis did not increase. Rather, Pb exposure maintained the survival of cortical precursors, as the progressive apoptosis occurring under control conditions was markedly reduced by the metal. Additionally, neuritic process initiation and outgrowth increased in a concentration-dependent manner, with processes four times as abundant on day 1 and twice as long on day 2. These results suggest that brief exposure to lead during neurogenesis directly affects cell survival and process development, potentially altering cortical arrangement. Consequently, alterations in neural circuitry may underlie some of the neurological effects of Pb exposure during brain development.

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Section: Discussioncontrasting

confidence: 85%

“…A study of the effects of Pb directly on cortical neurons, however, may be informative, since glial cells appear to be critical targets and modulators of metal toxicity in neuronal populations (Tiffany-Castiglioni et al, 1989;Tiffany-Castiglioni and Qian, 2001;Lindahl et al, 1999).…”

mentioning

confidence: 99%

Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Davidovics¹,

DiCicco‐Bloom²

2005

J. Neurosci. Res.

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“…While culture models indicate that MeHg alters neuronal precursor proliferation, in vivo changes in cell proliferation may reflect not only neuronal but also glial susceptibility (Garg and Chang 2006) to the toxicant. In addition, glial cells alter markedly the sensitivity of neurons in culture to metal toxicants, including both MeHg (Aschner, 1996;Shanker et al, 2003;Morken et al, 2005) and lead (Tiffany-Castiglioni and Qian, 2001;Zurich et al, 2002). Also, while glutathione may play a protective role following oxidative stress, both regions exhibit comparable levels of antioxidant defenses that protect cells from neurotoxicant insults (Li et al, 1996).…”

Section: Mehg Has Rapid Differential Effects On Proliferation In Devmentioning

confidence: 99%

Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E

Burke

Cheng

et al. 2006

NeuroToxicology

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The developing brain is highly sensitive to methylmercury (MeHg). Still, the initial changes in cell proliferation that may contribute to long-term MeHg effects are largely undefined. Our previous studies with growth factors indicate that acute alterations of G1/S phase transition can permanently affect cell numbers and organ size. Therefore, we determined whether an environmental toxicant could also impact brain development with rapid (6-7h) effects on DNA synthesis and cell cycle machinery in neuronal precursors. In vivo studies in newborn rat hippocampus and cerebellum, two regions of postnatal neurogenesis, were followed by in vitro analysis of two precursor models, cortical and cerebellar cells, focusing on the proteins that regulate G1/S transition. In postnatal day 7 (P7) pups, a single subcutaneous injection of MeHg (3μg/g) acutely (7h) decreased DNA synthesis in the hippocampus by 40% and produced long-term (2 weeks) reductions in total cell number, estimated by DNA quantification. Surprisingly, cerebellar granule cells were resistant to MeHg effects in vivo at comparable tissue concentrations, suggesting region-specific differences in precursor populations. In vitro, MeHg altered proliferation and cell viability, with DNA synthesis selectively inhibited at an early timepoint (6h) corresponding to our in vivo observations. Considering that G1/ S regulators are targets of exogenous signals, we used a well-defined cortical cell model to examine MeHg effects on relevant cyclin dependent kinases (CDK) and CDK inhibitors. At 6h, MeHg decreased by 75% levels of cyclin E, a cell cycle regulator with roles in proliferation and apoptosis, without altering p57, p27, or CDK2 nor levels of activated caspase 3. In aggregate, our observations identify the G1/S transition as an early target of MeHg toxicity and raise the possibility that cyclin E degradation contributes to both decreased proliferation and eventual cell death.

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“…Thus, one may consider manganese as an intracellular neuronal contrast agent for functionally active brain systems, while Cr(VI) serves as an extracellular "surface" agent that labels the myelin lipids of all accessible WM structures. In view of the fact that no histochemical method is available to demonstrate manganese in tissues (12), functional mapping of neural pathways by manganese-enhanced MRI (11,13) may now be complemented by outlining WM tracts with use of Cr(VI)-induced MRI contrast.…”

Section: Chromium-enhanced Mri Of White Mattermentioning

confidence: 99%

Chromium(VI) as a novel MRI contrast agent for cerebral white matter: Preliminary results in mouse brain in vivo

Watanabe

Tammer

Boretius

et al. 2006

Magnetic Resonance in Med

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This work demonstrates that intraventricular microinjections of a low dose of potassium dichromate (0.4 L of 10 mM solution) yield a specific contrast enhancement of white matter (WM) tracts in T 1 -weighted 3D MRI of mouse brain in vivo. Pronounced and persistent signal increases (40 -100% at 24 hr after injection) were observed in the corpus callosum, anterior commissure, fornix, and stria medullaris, as well as in the mammillothalamic tract and fasciculus retroflexus. These results suggest that the extracellular diffusion of diamagnetic chromium(VI) (Cr(VI)) after injection is followed by a tissue-specific reduction to paramagnetic Cr(V) and ( In neuroanatomy, specific chemical reactions of lipids exposed to aqueous solutions of potassium dichromate (K 2 Cr 2 O 7 with chromium in redox state Cr(VI)) have been used for histological staining of myelin. For example, in a previous study based on Weigert-Smith-Dietrich procedures, myelin sheaths in white matter (WM) tracts in rat brain were identified by controlled chromation of lipids, which was accompanied by a simultaneous reduction of Cr(VI) (1). The present work attempts to exploit such principles for cerebral MRI of WM. The idea is based on the assumption that a reduction of diamagnetic Cr(VI) to paramagnetic Cr(V) and Cr(III) by lipid oxidation causes a shortening of the T 1 relaxation time of surrounding water and/or lipid protons.Using sodium dichromate to study the metabolism of chromium species in biochemical reactions occurring on the skin of living rats, Liu and coworkers (2) demonstrated the potential of Cr(VI) for in vivo EPR spectroscopy. Similarly, the formation of Cr(V) and Cr(III) was detected by MRI after injection of sodium dichromate in the kidney and liver of a mouse in vivo (3), and of potassium chromate in the lung of a rat postmortem (4). The purposes of this first Cr(VI)-enhanced MRI study of mouse brain in vivo were to 1) examine whether a direct injection of a small amount of Cr(VI) induces a contrast enhancement detectable by T 1 -weighted 3D MRI, 2) determine the structures highlighted in the intact living brain, and 3) discuss putative histochemical and physiological mechanisms and how they differ from other paramagnetic MRI contrast agents.

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Astroglia as Metal Depots: Molecular Mechanisms for Metal Accumulation, Storage and Release

Cited by 140 publications

References 104 publications

Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Moderate lead exposure elicits neurotrophic effects in cerebral cortical precursor cells in culture

Methylmercury elicits rapid inhibition of cell proliferation in the developing brain and decreases cell cycle regulator, cyclin E

Chromium(VI) as a novel MRI contrast agent for cerebral white matter: Preliminary results in mouse brain in vivo

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