Chapter 19: Ultrastructural immunocytochemical observations on the localization, metabolism and transport of glutamate in normal and ischemic brain tissue

Storm‐Mathisen, Jon; Danbolt, N; Rothe, Fritz; Torp, Reidun; Zhang, N.; Aas, Jan-Erik; Kanner, Baruch I.; Langmoen, I. A.; Ottersen, Ole Petter

doi:10.1016/s0079-6123(08)61753-7

Cited by 81 publications

(50 citation statements)

References 77 publications

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“…Second, incubation with blocking peptides completely abolished the specific staining. Moreover, the reproducibility of the labeling in each case was high and allowed us to assess quantitatively the distribution of EGFR and PDGFRa in different subcellular compartments (Blackstad et al, 1990;Ottersen, 1989;Shupliakov et al, 1992;Storm-Mathisen et al, 1992). We also found that the PDGFRa expression pattern in fibroblasts in our experiment was identical to what has been reported previously (Bostrom et al, 1996;Ohba et al, 1994;Schneider et al, 2005).…”

Section: Discussionsupporting

confidence: 85%

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

Danilov

Gomes-Leal

Ahlenius

et al. 2008

Glia

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Neural stem cells (NSCs) in the subventricular zone (SVZ) continuously generate olfactory bulb interneurons in the adult rodent brain. Based on their ultrastructural and antigenic properties, NSCs, transient amplifying precursor cells, and neuroblasts (B, C, and A cells, respectively) have been distinguished in mouse SVZ. Here, we aimed to identify these cell types in rat SVZ ultrastructurally and at the light microscopy level, and to determine the antigenic properties of each cell type using gold and fluorescence immunolabeling. We found astrocytes with single cilia (NSCs, correspond to B cells) and neuroblasts (A cells). We also observed mitotic cells, ependymal cells, displaced ependymal cells, and mature astrocytes. In contrast, transient amplifying precursor cells (C cells) were not detected. The NSCs and neuroblasts had epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor alpha (PDGFRa) expressed on the ciliary apparatus and were the only cell types incorporating the proliferation marker BrdU. Throughout mitosis, EGFR and PDGFRa were associated with the microtubule of the mitotic spindle. Ependymal and displaced ependymal cells also expressed EGFR and PDGFRa on their cilia but did not incorporate BrdU. Our findings indicate that the NSCs in adult rat SVZ give rise directly to neuroblasts. During mitosis, the NSCs disassemble the primary cilium and symmetrically distribute EGFR and PDGFRa among their progeny. V

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Section: Discussionsupporting

confidence: 85%

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

Danilov

Gomes-Leal

Ahlenius

et al. 2008

Glia

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“…Astrocytes are integrally involved in metabolic and ionic homeostasis, inflammatory responses, and control of extracellular glutamate levels (Aas et al, 1993;Hertz and Zielke, 2004;Hertz et al, 1999;Storm-Mathisen et al, 1992;Torp et al, 1994). Astrocytes also produce neurotrophic factors that promote neuronal survival and provide neurons with precursors for glutathione biosyn-thesis, which is necessary to combat oxidative stress (Dringen, 2000;Drukarch et al, 1997;Makarov et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Danilov

Fiskum

2008

Glia

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Astrocyte dysfunction and death accompany cerebral ischemia/reperfusion and possibly compromise neuronal survival. Animal studies indicate that neuronal death, neurologic injury, and oxidative molecular modifications are worse in animals exposed to hyperoxic compared to normoxic ventilation during reperfusion after global cerebral ischemia. It is unknown, however, whether ambient O 2 affects brain cell survival using in vitro ischemia paradigms where mechanisms of injury to specific cell types can be more thoroughly investigated. This study tested the hypothesis that compared with the supraphysiological level of 20% O 2 normally used in cell culture, lower, more physiological O 2 levels protect astrocytes from death following oxygen and glucose deprivation. Primary rat cortical astrocytes were cultured under either 7 or 20% O 2 , exposed to O 2 , and glucose deprivation for 4 h, and then exposed to normal medium under either 7 or 20% O 2 . Cell death and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine immunoreactivities were assessed at different periods of reoxygenation. Astrocytes exposed to low levels of O 2 during reoxygenation undergo less death and exhibit lower levels of protein nitration and nucleic acid oxidation when compared with those under high levels of O 2 during reoxygenation. These results support the hypothesis that the 20% O 2 normally used in cell culture exacerbates astrocyte death and oxidative stress in an in vitro ischemia/reperfusion model compared to levels that more closely approximate those that exist in vivo.

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“…Although terminals are generally believed to have much higher glutamate levels than astrocytes, there is, as far as we are aware of, no comprehensive overview of the glutamate concentrations in the various cellular compartments in different brain regions of wildtype animals. It is, however, possible to do some very rough estimates by combining histology data from normal rats (Nafstad and Blackstad, 1966;Lehre and Danbolt, 1998) with available information on glutamate distribution (Ottersen, 1989;Storm-Mathisen and Ottersen, 1990;Torp et al, 1991;Storm-Mathisen et al, 1992;Ottersen et al, 1992;Ottersen et al, 1996). Based on this studies is seems reasonable to conclude that around 10 % of tissue glutamate is in astroglia, 70 % in glutamatergic nerve terminals and the remainder in other parts of the neurons.…”

Section: Heteroexchange Is Not Substantially Faster Than Net Uptakementioning

confidence: 97%

Neuronal vs glial glutamate uptake: Resolving the conundrum

Danbolt

Furness

Zhou

2016

Neurochemistry International

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181

158

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Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However, the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox. ABBREVIATIONSCre, Cyclization recombinase (Le and Sauer, 2000); EAAC1, glutamate transporter (EAAT3; slc1a1; Kanai and Hediger, 1992; Bjørås et al., 1996); EAAT, excitatory amino acid transporter (synonym to glutamate transporter); GABA, γ-aminobutyric acid; GLAST, rat glutamate transporter (EAAT1; slc1a3; Storck et al., 1992;Tanaka, 1993a); GLT-1, rat glutamate transporter (EAAT2; slc1a2; Pines et al., 1992); GLUL, glutamine synthetase; TBOA, DL-threo-β-benzyloxyaspartate AbstractNeither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that astrocytes and neurons express glutamate transporters. The relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) an hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox.

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Chapter 19: Ultrastructural immunocytochemical observations on the localization, metabolism and transport of glutamate in normal and ischemic brain tissue

Cited by 81 publications

References 77 publications

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

Ultrastructural and antigenic properties of neural stem cells and their progeny in adult rat subventricular zone

Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation

Neuronal vs glial glutamate uptake: Resolving the conundrum

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