Abstract
Stem cell technology promises new and rapid advances in cell therapy and drug discovery. Clearly, the value of this approach will be limited by the differentiated functions displayed by the progeny of stem cells. The foetal and adult central nervous system (CNS) harbour stem cells that can be expanded in vitro and differentiate into immature neurons and glia. Surprisingly, we do not know if neurons derived from stem cells form synapses, a definitive feature of neuronal function. Neuronal differentiation is a complex process and in this paper we establish conditions that permit extensive maturation of neurons in the presence of neurotrophins. These conditions permit the differentiation of rat hippocampal stem cells into both excitatory (glutamatergic) and inhibitory (GABAergic) neurons. The proportion of excitatory and inhibitory synapses was strongly influenced by specific neurotrophins, and these responses reflect the region of origin of the stem cells in the brain. These data show that stem cells can be used to study mechanisms of excitation and inhibition in the nervous system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Brain-Derived Neurotrophic Factor / pharmacology*
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / analysis
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Cell Culture Techniques / methods
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Cell Differentiation / drug effects
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Cell Lineage
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Cells, Cultured / drug effects
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology
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GABA Antagonists / pharmacology
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Glutamic Acid / pharmacology
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Hippocampus / cytology*
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Immunoenzyme Techniques
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Intermediate Filament Proteins / metabolism
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Nerve Growth Factor / pharmacology*
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Nerve Growth Factors / pharmacology*
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Nerve Tissue Proteins / metabolism
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Nestin
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Neurons / classification
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Neurons / cytology*
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Neurons / drug effects
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Neurotrophin 3 / pharmacology*
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Phosphoprotein Phosphatases / metabolism
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Rats
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Receptor, trkB / metabolism
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Receptor, trkC / metabolism
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Receptors, AMPA / metabolism
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Stem Cells / cytology*
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Stem Cells / drug effects
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Synapses / drug effects
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Synapses / physiology
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Synapsins / metabolism
Substances
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Brain-Derived Neurotrophic Factor
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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GABA Antagonists
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Intermediate Filament Proteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Nes protein, rat
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Nestin
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Neurotrophin 3
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Receptors, AMPA
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Synapsins
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Glutamic Acid
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Nerve Growth Factor
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Receptor, trkB
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Receptor, trkC
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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microtubule-associated protein-2 phosphatase
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Phosphoprotein Phosphatases
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neurotrophin 4
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glutamate receptor ionotropic, AMPA 2