Neuroblastoma and glioma cell cultures in studies of neurologic functions: the clinician's Rosetta Stone?

Research output: Contribution to journalArticle

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Abstract

The neuroblastoma C 1300 cell line derived from the ajax strain of mouse has been in culture for over 8,000 cell generations and still retains many properties of differentiated in vivo mammalian neurons, including possessing choline acetyltransferase, acetylcholinesterase, catechol O methyltransferase, monoamine oxidase, neurites containing neurotubules, neurofilaments, and dense core vesicles, tyrosine hydroxylase, aromatic amino acid decarboxylase, and dopamine beta hydroxylase for the generating action potentials. It has been demonstrated that neuronal enzymes concerned with neurotransmitter synthesis or metabolism rise in specific activity and reach a maximum when the cultures are postmitotic and most morphologically differentiated with long neurites and multiple cell contacts. Acetylcholinesterase increased under differentiating circumstances 25 fold, choline acetyltransferase sixfold, and tyrosine hydroxylase 30 fold compared with rapidly dividing undifferentiated cells in culture. A later phase in neuronal differentiation in vivo after axonal and dendritic proliferation and synapse formation is the induction of neurotransmitter biosynthesis and metabolism. In cell culture, highest levels of the neurotransmitter synthesizing enzymes, choline acetyltransferase and tyrosine hydroxylase are achieved in postmitotic highly differentiated cells in culture. Neuroblastoma and glioma cells in culture can be induced to differentiate by the addition of a variety of agents including: 5 bromodeoxyuridine, dibutyryl cyclic adenosine 3'-5' monophosphate (db cyclic AMP), and prostaglandins (PGE1 and PGE2) with the simultaneous induction of choline acetyltransferase or tyrosine hydroxylase. These events involve the activation of protein kinases with subsequent phosphorylation of nuclear histone protein. Further, there are changes in the concentration of the 4 species of nuclear histone proteins during development in culture and these changes occur before increases in specific activity of the neurotransmitter synthetic enzymes in the cytoplasm and thus may be important regulatory phenomena. Both neuroblastoma and glioma cell lines possess high affinity uptake permases for the ultimate inactivation of norepinephrine, dopamine, serotonin, taurine, glutamate, glycine, and gamma amino butyric acid. De novo synapse formation between neuroblastoma and muscle cells has been demonstrated and has proved a valuable model system to investigate neurotransmitter biochemistry. Neuroblast and glial clonal lines only recently have been applied successfully to problems of basic neurology; the future looks bright for this approach to continue to provide molecular insights into differentiation and disease.

Original languageEnglish (US)
Pages (from-to)105-108
Number of pages4
JournalNeurology
Volume27
Issue number2
StatePublished - 1977

Fingerprint

Neuroblastoma
Glioma
Choline O-Acetyltransferase
Nervous System
Neurotransmitter Agents
Tyrosine 3-Monooxygenase
Cell Culture Techniques
Neurites
Acetylcholinesterase
Nuclear Proteins
Histones
Synapses
Enzymes
Aromatic-L-Amino-Acid Decarboxylases
Catechol O-Methyltransferase
Cell Line
Dopamine beta-Hydroxylase
Butyric Acid
Intermediate Filaments
Alprostadil

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neuroblastoma and glioma cell cultures in studies of neurologic functions : the clinician's Rosetta Stone? / Rosenberg, R. N.

In: Neurology, Vol. 27, No. 2, 1977, p. 105-108.

Research output: Contribution to journalArticle

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abstract = "The neuroblastoma C 1300 cell line derived from the ajax strain of mouse has been in culture for over 8,000 cell generations and still retains many properties of differentiated in vivo mammalian neurons, including possessing choline acetyltransferase, acetylcholinesterase, catechol O methyltransferase, monoamine oxidase, neurites containing neurotubules, neurofilaments, and dense core vesicles, tyrosine hydroxylase, aromatic amino acid decarboxylase, and dopamine beta hydroxylase for the generating action potentials. It has been demonstrated that neuronal enzymes concerned with neurotransmitter synthesis or metabolism rise in specific activity and reach a maximum when the cultures are postmitotic and most morphologically differentiated with long neurites and multiple cell contacts. Acetylcholinesterase increased under differentiating circumstances 25 fold, choline acetyltransferase sixfold, and tyrosine hydroxylase 30 fold compared with rapidly dividing undifferentiated cells in culture. A later phase in neuronal differentiation in vivo after axonal and dendritic proliferation and synapse formation is the induction of neurotransmitter biosynthesis and metabolism. In cell culture, highest levels of the neurotransmitter synthesizing enzymes, choline acetyltransferase and tyrosine hydroxylase are achieved in postmitotic highly differentiated cells in culture. Neuroblastoma and glioma cells in culture can be induced to differentiate by the addition of a variety of agents including: 5 bromodeoxyuridine, dibutyryl cyclic adenosine 3'-5' monophosphate (db cyclic AMP), and prostaglandins (PGE1 and PGE2) with the simultaneous induction of choline acetyltransferase or tyrosine hydroxylase. These events involve the activation of protein kinases with subsequent phosphorylation of nuclear histone protein. Further, there are changes in the concentration of the 4 species of nuclear histone proteins during development in culture and these changes occur before increases in specific activity of the neurotransmitter synthetic enzymes in the cytoplasm and thus may be important regulatory phenomena. Both neuroblastoma and glioma cell lines possess high affinity uptake permases for the ultimate inactivation of norepinephrine, dopamine, serotonin, taurine, glutamate, glycine, and gamma amino butyric acid. De novo synapse formation between neuroblastoma and muscle cells has been demonstrated and has proved a valuable model system to investigate neurotransmitter biochemistry. Neuroblast and glial clonal lines only recently have been applied successfully to problems of basic neurology; the future looks bright for this approach to continue to provide molecular insights into differentiation and disease.",
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