A Role for Astrocytes in Glucose Delivery to Neurons?

Forsyth, Rob; Fray, Ann; Boutelle, Martyn G.; Fillenz, Marianne; Middleditch, Claire; Burchell, Ann

doi:10.1159/000111429

Cited by 65 publications

(34 citation statements)

References 51 publications

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“…Our findings regarding the enhanced susceptibility of astrocytes to UCB toxicity may be of great relevance because glial cells seem to play a key role in the maintenance of brain function (23). In addition, interdependence of astrocytes and neurons has been demonstrated in studies reporting that astrocytes deliver glutamine and glucose to neurons (24,49), and protect neuronal cells from toxic agents (25,50,51).…”

mentioning

confidence: 61%

“…Although neurons have been suggested as more susceptible than astrocytes (13), more recent reports describe compromised astrocyte function following UCB interaction (19 -22). Evidence is also arising on the influence of astrocytes in neuronal function, metabolism, and survival (23)(24)(25)(26). The role of astrocytes on UCB toxicity is further reinforced by electron microscopic and autoradiographic studies on experimental kernicterus, indicating that these cells represent the main transporters of UCB from blood to neurons and are also involved in the release of waste products from UCB damaged neurons (27,28).…”

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confidence: 99%

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Rat Cultured Neuronal and Glial Cells Respond Differently to Toxicity of Unconjugated Bilirubin

2002

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High levels of unconjugated bilirubin (UCB) can be neurotoxic. Nevertheless, the mechanism of UCB interaction with neural cells is still unknown. This study investigates whether cultured rat neurons and astrocytes respond differently to UCB exposure. UCB toxicity was evaluated by lactate dehydrogenase release, induction of apoptosis, cytoskeleton degeneration, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and glutamate uptake. Primary cultures of rat brain astrocytes and neurons were incubated at 37°C with 85.5 M UCB plus 28.5 M albumin for 4 h. In assays of glutamate uptake, cells were exposed to 80 -120 M UCB plus 100 M albumin for 15 min. The results showed that after incubation with 85.5 M UCB, lactate dehydrogenase release was greater in neurons than in astrocytes (38% versus 14%, p Ͻ 0.05). Also, levels of apoptosis were markedly enhanced in neurons (29% versus 19%, p Ͻ 0.01). In accordance, neuronal cytoskeleton disassembly was evident during incubation with 85.5 M UCB, whereas equivalent effects on astrocytes required as much as 171 M. Conversely, inhibition of MTT metabolism and glutamate uptake by UCB was more pronounced in astrocytes than in neurons (74% versus 60%, p Ͻ 0.05 and 41% to 56% versus 25% to 33%, p Ͻ 0.05, respectively). In conclusion, the study demonstrates that astrocytes are more susceptible to inhibition of glutamate uptake and MTT reduction by UCB, whereas neurons are more sensitive to cell death by necrosis or apoptosis. These results suggest that UCB is toxic to both astrocytes and neurons, although through distinct pathways. Neonatal jaundice is a very common predicament, usually requiring therapeutic intervention in early life. The significance of neonatal hyperbilirubinemia can vary from a minor nontoxic phenomenon to death by kernicterus (1-3). In contrast to kernicterus, where permanent lesions or death are likely to occur (4 -6), bilirubin encephalopathy can result in transient or sometimes definitive effects of UCB toxicity, such as auditory and visual impairment (7-9). However, the mechanisms of bilirubin encephalopathy and kernicterus remain unclear.Nerve cells are the main target for UCB cytotoxicity. In fact, several effects of UCB toxicity to neurons have been reported either in brain sections (10 -12), cultured cell lines (13, 14), or isolated nerve terminals (15-18). Although neurons have been suggested as more susceptible than astrocytes (13), more recent reports describe compromised astrocyte function following UCB interaction (19 -22). Evidence is also arising on the influence of astrocytes in neuronal function, metabolism, and survival (23-26). The role of astrocytes on UCB toxicity is further reinforced by electron microscopic and autoradiographic studies on experimental kernicterus, indicating that these cells represent the main transporters of UCB from blood to neurons and are also involved in the release of waste products from UCB damaged neurons (27,28).We have previously shown that UCB significantly reduces glutamate uptake in ...

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confidence: 61%

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confidence: 99%

Rat Cultured Neuronal and Glial Cells Respond Differently to Toxicity of Unconjugated Bilirubin

2002

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“…A trafficking pathway for delivery of nutrients and metabolites between astrocytes and neurons is supported by previous studies. Astrocytes have been implicated in the delivery of glucose and lactate to neurons (19) and are known to play an important role in the uptake and recycling of neuronally released glutamate (20). In this respect it is of interest that glutamine synthetase in human cerebral cortical astrocytes is localized in a manner that closely resembles the perisynaptic astrocytic localization of NPC1 in this study (16).…”

Section: Discussionmentioning

confidence: 87%

Localization of Niemann–Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann– Pick type C disease

Suresh

Kumar

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

158

102

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Niemann-Pick type C disease (NP-C) is an inherited neurovisceral lipid storage disorder characterized by progressive neurodegeneration. Most cases of NP-C result from inactivating mutations of NPC1, a recently identified member of a family of genes encoding membrane-bound proteins containing putative sterol sensing domains. By using a specific antipeptide antibody to human NPC1, we have here investigated the cellular and subcellular localization and regulation of NPC1. By light and electron microscopic immunocytochemistry of monkey brain, NPC1 was expressed predominantly in perisynaptic astrocytic glial processes. At a subcellular level, NPC1 localized to vesicles with the morphological characteristics of lysosomes and to sites near the plasma membrane. Analysis of the temporal and spatial pattern of neurodegeneration in the NP-C mouse, a spontaneous mutant model of human NP-C, by amino-cupric-silver staining, showed that the terminal fields of axons and dendrites are the earliest sites of degeneration that occur well before the appearance of a neurological phenotype. Western blots of cultured human fibroblasts and monkey brain homogenates revealed NPC1 as a 165-kDa protein. NPC1 levels in cultured fibroblasts were unchanged by incubation with low density lipoproteins or oxysterols but were increased 2-to 3-fold by the drugs progesterone and U-18666A, which block cholesterol transport out of lysosomes, and by the lysosomotropic agent NH 4 Cl. These studies show that NPC1 in brain is predominantly a glial protein present in astrocytic processes closely associated with nerve terminals, the earliest site of degeneration in NP-C. Given the vesicular localization of NPC1 and its proposed role in mediating retroendocytic trafficking of cholesterol and other lysosomal cargo, these results suggest that disruption of NPC1-mediated vesicular trafficking in astrocytes may be linked to neuronal degeneration in NP-C.

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“…They scattered throughout the tectum and substantia nigra within ventrolateral tegmentum. In addition to contributing to the metabolism and neurotransmission (Forsyth et al 1996), astrocytes may be involved in inducing specific neurochemical phenotypes. Investigation revealed that induction of a ventral mesencephalic dopaminergic phenotype could be fulfilled by diffusible factors derived from local subtype of astrocytes (Wagner et al 1999).…”

Section: The Corresponding Roles Played By Astrocytes In Mesencephalonmentioning

confidence: 99%

Characterization of adult neurogenesis in lizardPhrynocephalus vlangalii(Agamidae: Reptilia)

Shao

Fan

et al. 2012

Italian Journal of Zoology

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Adult neurogenesis, a process of giving rise to neurons and glia from progenitors residing in restricted regions of the adult central nervous system (CNS) throughout life, varies considerably across species. The role of adult neurogenesis in reptiles, the amniotic vertebrates that possess spontaneous regenerative capacity is less known. In the present study, we used Phrynocephalus vlangalii -a typical reptile in northwest of China to investigate the cell proliferation and general pattern of glial fibrillary acidic protein (GFAP)-immunoreactivity in the brain of lizard. Compared with mammals, the brains of P. vlangaliiowned have simpler cytoarchitectonical patterns but a more widespread neurogenesis. Bromodeoxyuridine (BrdU)-labeled cells were mostly distributed in the ventricular zone of lateral ventricle with cell proliferation highest in the region referred to as anterior olfactory nucleus (AON). In addition, GFAP-immunostaining demonstrated differences in element, abundance and distribution. GFAP-positive cells were fundamentally represented by radial glial structures in telencephalon, diencephalon and mesencephalon. Furthermore, an intriguing finding was the emergence of GFAP-positive, star-shaped cells in the mesencephalon. We conclude that the cell proliferation and corresponding functions of glial lineage cells in lizards are closely implicated with phylogenetic development. Hence, reptiles provide excellent access for extracting core mechanisms of adult neurogenesis, which lays a good foundation to study the effect of different stimuli and exposure on the adult neurogenesis of reptiles.

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A Role for Astrocytes in Glucose Delivery to Neurons?

Cited by 65 publications

References 51 publications

Rat Cultured Neuronal and Glial Cells Respond Differently to Toxicity of Unconjugated Bilirubin

Rat Cultured Neuronal and Glial Cells Respond Differently to Toxicity of Unconjugated Bilirubin

Localization of Niemann–Pick C1 protein in astrocytes: Implications for neuronal degeneration in Niemann– Pick type C disease

Characterization of adult neurogenesis in lizardPhrynocephalus vlangalii(Agamidae: Reptilia)

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