Electrophysiological Properties of Mitogen-Expanded Adult Rat Spinal Cord and Subventricular Zone Neural Precursor Cells

Liu, Rong-Huan; Morassutti, Dante J.; Whittemore, Scott R.; Sosnowski, Jeffrey; Magnuson, David S.K.

doi:10.1006/exnr.1999.7078

Cited by 45 publications

(29 citation statements)

References 51 publications

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“…This finding is in apparent contrast to previous studies using embryonic rat hippocampal progenitors grown under different culture conditions in which spontaneous activity was not observed but in which activity could be evoked with glutamate agonists (3,4). Evoked activity has also been reported in neurons derived from precursors from other central nervous system regions (4,19,(31)(32)(33). Previous studies were performed at the single-cell level by using patch-clamp recordings (4,19,(31)(32)(33) or with measurement of alterations in intracellular calcium levels (19,20), as opposed to the MEAs used in the present study, which measured network activity from multiple cells.…”

Section: Discussioncontrasting

confidence: 97%

“…Evoked activity has also been reported in neurons derived from precursors from other central nervous system regions (4,19,(31)(32)(33). Previous studies were performed at the single-cell level by using patch-clamp recordings (4,19,(31)(32)(33) or with measurement of alterations in intracellular calcium levels (19,20), as opposed to the MEAs used in the present study, which measured network activity from multiple cells. It is noteworthy that the percentage of cells capable of firing evoked action potentials in previous reports was highly variable.…”

Section: Discussionmentioning

confidence: 65%

“…N-CAM and BDNF appear equally efficacious in neural progenitor differentiation in terms of the numbers of neurons produced, the phenotype of neurons generated, and physiological activity of progenitor-derived neurons. In the presence of FGF2, the number of progenitors was significantly higher under all treatment conditions, suggesting that progenitor expansion may be limited by early removal of FGF2, a protocol often used in inducing differentiation of hippocampal stem cells (4,19,(31)(32)(33). BDNF and N-CAM effectively promoted differentiation even in the presence of FGF2, recommending the inclusion of this growth factor during the culture of progenitors.…”

Section: Discussionmentioning

confidence: 96%

“…It is noteworthy that the percentage of cells capable of firing evoked action potentials in previous reports was highly variable. For example, only 6% of neurons derived from subventricular zone progenitors fired action potentials in response to current injection, whereas 64% of spinal cord-derived cells did so (31). Action potentials were elicited in 30% of neurons derived from adult hippocampal progenitors (33).…”

Section: Discussionmentioning

confidence: 99%

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Cultured rat hippocampal neural progenitors generate spontaneously active neural networks

Mistry

Keefer

Cunningham

et al. 2002

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

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We previously demonstrated that the neural cell adhesion molecule (N-CAM) inhibited the proliferation of cultured rat hippocampal progenitor cells and increased the number of neurons generated. We demonstrate here that the continued presence of fibroblast growth factor 2 along with N-CAM or brain-derived neurotrophic factor over 12 days of culture greatly increased the number of both progenitors and neurons. These progenitorderived neurons expressed neurotransmitters, neurotransmitter receptors, and synaptic proteins in vitro consistent with those expressed in the mature hippocampus. Progenitor cells cultured on microelectrode plates formed elaborate neural networks that exhibited spontaneously generated action potentials after 21 days. This activity was observed only in cultures grown in the presence of fibroblast growth factor 2 and either N-CAM or brain-derived neurotrophic factor. Analysis of neuronal activity after various pharmacological treatments indicated that the networks formed functional GABAergic and glutamatergic synapses. We conclude that mitogenic growth factors can synergize with N-CAM or neurotrophins to generate spontaneously active neural networks from neural progenitors.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cultured rat hippocampal neural progenitors generate spontaneously active neural networks

Mistry

Keefer

Cunningham

et al. 2002

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

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“…Voltagedependent sodium currents were detected in cultured NPCs isolated from adult human hippocampus (34), suggesting that these cells might have the ability to spike. In addition, NPCs purified from the SVZ of adult rats displayed repetitive spiking in response to exogenous glutamate application (15). Definitive evidence of a functional neuronal phenotype came from studies carried out with progenitors isolated from adult rat hippocampus.…”

Section: Figure 2 Neurogenesis and The Synaptic Plasticity And Memormentioning

confidence: 99%

A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function

Schinder

Gage

2004

Physiology

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The functional relevance of adult hippocampal neurogenesis has long been a matter of intense experimentation and debate, but the precise role of new neurons has not been sufficiently elaborated. Here we propose a hypothesis in which specific features of newly generated neurons contribute to hippocampal plasticity and function and discuss the most recent and relevant findings in the context of the proposed hypothesis.

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Lineage restriction of neuroepithelial precursor cells from fetal human spinal cord

et al. 1999

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In the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF2), neuroepithelial precursor cells from dissociated fetal human spinal cord are mitotically active and form free-floating spheres of undifferentiated cells. Proliferating cells were obtained in approximately 40% of preparations with each mitogen, were immunoreactive for the intermediate filament nestin, and did not express neuronal- or glial-specific markers. Early passage neuroepithelial precursor cells were pluripotent and differentiated into neurons expressing MAP2a,b, NF-M, and TuJ1, and GFAP-positive astrocytes; however, oligodendrocytes were never seen. As the cells were passaged from P0 to P4, the percentage of differentiating neurons significantly decreased and the prevalence of astrocytes significantly increased. While the majority of cell populations from individual preparations stopped proliferating between 3 and 6 passages, two expanding cell lines have been successfully expanded in EGF and FGF2 for over 25 passages and have been maintained in culture for over one year. These cells express nestin and not other cell-specific lineage markers. When differentiated, these neuroepithelial cell lines differentiate only into astrocytes, showing no expression of any neuronal marker. These data suggest that continued passage under these conditions preferentially selects for spinal cord neural precursors that are restricted to the astrocytic lineage. Despite the lineage restriction of later passage cell populations, these results provide a rationale for future investigation into the lineage potential of these cells in vivo following transplantation into the adult CNS, potentially as a therapeutic approach for traumatic injury and neurodegenerative disease.

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Electrophysiological Properties of Mitogen-Expanded Adult Rat Spinal Cord and Subventricular Zone Neural Precursor Cells

Cited by 45 publications

References 51 publications

Cultured rat hippocampal neural progenitors generate spontaneously active neural networks

Cultured rat hippocampal neural progenitors generate spontaneously active neural networks

A Hypothesis About the Role of Adult Neurogenesis in Hippocampal Function

Lineage restriction of neuroepithelial precursor cells from fetal human spinal cord

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