Conditionally Immortalized Neural Cell Lines: Potential Models for the Study of Neural Cell Function

Bongarzone, Ernesto R.; Foster, Lyndon M.; Byravan, Sujatha; Verity, A. Neil; Landry, Charles F.; Schonmann, Vilma; Amur‐Umarjee, Shashi; Campagnoni, Anthony T.

doi:10.1006/meth.1996.0126

Cited by 38 publications

(43 citation statements)

References 2 publications

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“…OLP cells were prepared as described previously from primary glial cultures from MLD or wild-type animals (Gard and Pfeiffer, 1989;Louis at al, 1992;Bongarzone et al, 1996). Cells were grown in glial defined medium consisting of DMEM/F12 supplemented with 5 mg/L insulin, 16.1 mg/L putrescine, 50 mg/L transferrin, 0.8 g/ml sodium selenite, and 2.2 g/l sodium bicarbonate.…”

Section: Methodsmentioning

confidence: 99%

Oligodendroglial Progenitor Cell Therapy Limits Central Neurological Deficits in Mice with Metachromatic Leukodystrophy

et al. 2006

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This work describes the first successful oligodendrocyte-based cell therapy for presymptomatic arylsulfatase A (ARSA) null neonate mice, a murine model for human metachromatic leukodystrophy (MLD). We found that oligodendrocyte progenitors (OLPs) engrafted and survived into adulthood when transplanted in the neonatal MLD brain. Transplanted cells integrated nondisruptively, did not produce tumors, and survived as proteolipid protein-and MBP-positive postmitotic myelinating oligodendrocytes (OLs) intermingled with endogenous MLD OLs within the adult MLD white matter. Transplanted MLD mice had reduced sulfatide accumulation in the CNS, increased brain ARSA activity, and full prevention of the electrophysiological and motor deficits that characterize untreated MLD mice. Our results provide direct evidence that healthy OLPs can tolerate the neurotoxic accumulation of sulfatides that evolves during the postnatal development of the MLD brain and contribute to OL cell replacement to limit the accumulation of sulfatides and the evolution of CNS defects in this lysosomal storage disease mouse model.

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Section: Methodsmentioning

confidence: 99%

Oligodendroglial Progenitor Cell Therapy Limits Central Neurological Deficits in Mice with Metachromatic Leukodystrophy

et al. 2006

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“…Cell Culture-Conditionally immortalized cortical cells (CN1.4) from mice (35) were maintained at 33°C in Dulbecco's modified Eagle's medium High Glucose media (Irvine Scientific), supplemented with 8% heat-inactivated fetal bovine serum (Invitrogen), 2 mM L-glutamine (Invitrogen), 100 units/ml penicillin G, 100 g/ml streptomycin (Invitrogen). Stably transfected wild type tau and mutant R406W tau-expressing CN1.4 cells were maintained in media supplemented with 1 mg/ml hygromycin B (Roche Applied Science).…”

Section: Methodsmentioning

confidence: 99%

Mutant (R406W) Human Tau Is Hyperphosphorylated and Does Not Efficiently Bind Microtubules in a Neuronal Cortical Cell Model

Krishnamurthy

Johnson

2004

Journal of Biological Chemistry

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Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative disorder caused by mutations in the gene that encodes for tau, a microtubule-binding protein. Neuropathologically the disease is characterized by extensive neuronal loss in the frontal and temporal lobes and the filamentous accumulation of hyperphosphorylated tau. The R406W missense mutation was originally described in an American and a Dutch family. Although R406W tau is hyperphosphorylated in FTDP-17 cases, R406W tau expressed in cell model systems has not shown increased phosphorylation. The purpose of this study was to establish a neuronal model system in which the phosphorylation of R406W tau is increased and thus more representative of the in vivo situation. To accomplish this goal immortalized mouse cortical cells that express low levels of endogenous tau were stably transfected with human wild type or R406W tau. In this neuronal model R406W tau was more highly phosphorylated at numerous epitopes and showed decreased microtubule binding compared with wild type tau, an effect that could be reversed by dephosphorylation. In addition the expression of R406W tau in the cortical cells resulted in increased cell death as compared with wild type tau-expressing cells when the cells were exposed to an apoptotic stressor. These results indicate that in an appropriate cellular context R406W tau is hyperphosphorylated, which leads to decreased microtubule binding. Furthermore, expression of R406W tau sensitized cells to apoptotic stress, which may contribute to the neuronal cell loss that occurs in this FTDP-17 tauopathy.Frontotemporal dementia (FTD) 1 refers to a group of neurological disorders that are characterized clinically by progressive behavioral changes and neuropathologically by neuronal loss in the frontal and temporal lobes and the presence of filamentous deposits of abnormally hyperphosphorylated tau protein in neurons and/or glial cells (1-4). FTDs occur mainly as sporadic cases but also as familial forms with an autosomal dominant mode of inheritance and age-dependent penetrance (1). In 1998 it was demonstrated that several familial FTDs were due to mutations in the tau gene and have been referred to as frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17) (5-7). Since these initial discoveries, additional tau mutations have been described in frontotemporal dementia families, and presently over 25 mutations in the tau gene have been identified (8, 9). They include missense mutations in coding regions, amino acid deletions, and intronic mutations in the region following exon 10. The mutations may be divided into two main groups, those that affect alternative splicing of exon 10, leading to changes in the ratio of tau mRNAs with or without exon 10, and thus the proportion of tau with three microtubule binding repeats versus tau with four microtubule binding repeats, and missense mutations.Tau is a microtubule-associated protein that facilitates microtubule assembly an...

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“…Mixed rat glial cultures were prepared exactly as described in Cole and de Vellis [2001] and Bongarzone et al [1996]. Rat OPCs were isolated by a shaking procedure from 6-day-old glial cultures using the protocol described in Bongarzone et al [1996].…”

Section: Cell Culturementioning

confidence: 99%

<i>Notch1</i> and <i>Numb</i> Genes Are Inversely Expressed as Oligodendrocytes Differentiate

Givogri

Schonmann²,

Cole

et al. 2003

Dev Neurosci

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The Notch1 pathway plays a fundamental role during the establishment of cell fates in the central nervous system (CNS) by regulating neural cell differentiation. In oligodendrocytes (OLs), Notch1 activity prevents these cells from becoming terminally mature, thereby influencing CNS myelination. Little is known of how OLs regulate the expression of this receptor at the gene level or if OLs have mechanisms to control the level of intracellular activity of the Notch1 pathway. In this study, we have found that Notch1 gene expression was higher in proliferative OL progenitor cells (OPCs) and was reduced when cells were forced to withdraw from the cell cycle and became mature, indicating that Notch1 gene expression is developmentally regulated in OLs. We observed that the blockade of terminal differentiation of OPCs by incubation with Delta1, an activator of Notch1, was a dominant process and OL-differentiating signals such as thyroid hormone could not overcome this inhibition in culture. This suggests that a downregulation of the Notch1 pathway might be required to allow OPCs to enter terminal differentiation. We also provide evidence that OPCs and OLs express the Numb gene, a known negative regulator of Notch1 activity. In vivo, Numb was found in postnatal OLs from cerebellar and cerebral white matter. In vitro, Numb expression showed to be inversely correlated to that of Notch1, with higher levels of Numb proteins in mature OLs, in association with myelin-like membranes.

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Conditionally Immortalized Neural Cell Lines: Potential Models for the Study of Neural Cell Function

Cited by 38 publications

References 2 publications

Oligodendroglial Progenitor Cell Therapy Limits Central Neurological Deficits in Mice with Metachromatic Leukodystrophy

Oligodendroglial Progenitor Cell Therapy Limits Central Neurological Deficits in Mice with Metachromatic Leukodystrophy

Mutant (R406W) Human Tau Is Hyperphosphorylated and Does Not Efficiently Bind Microtubules in a Neuronal Cortical Cell Model

<i>Notch1</i> and <i>Numb</i> Genes Are Inversely Expressed as Oligodendrocytes Differentiate

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