Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation
Recent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996120302175 |
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| author | Elena Tantillo Eleonora Vannini Chiara Cerri Cristina Spalletti Antonella Colistra Chiara Maria Mazzanti Mario Costa Matteo Caleo |
| author_facet | Elena Tantillo Eleonora Vannini Chiara Cerri Cristina Spalletti Antonella Colistra Chiara Maria Mazzanti Mario Costa Matteo Caleo |
| author_sort | Elena Tantillo |
| collection | DOAJ |
| description | Recent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different subsets of cortical neurons, such as GABAergic interneurons, remains unexplored. Here, we directly compared the effects of optogenetic stimulation of pyramidal cells vs. fast-spiking, GABAergic neurons. In mice inoculated with GL261 cells into the motor cortex, we show that optogenetic stimulation of pyramidal neurons enhances glioma cell proliferation. In contrast, optogenetic stimulation of fast-spiking, parvalbumin-positive interneurons reduces proliferation as measured by BrdU incorporation and Ki67 immunolabelling. Since both principal cells and fast-spiking interneurons are directly activated by sensory afferent input, we next placed tumors in the occipital cortex to test the impact of visual stimulation/deprivation. We report that total lack of visual input via dark rearing enhances the density of proliferating glioma cells, while daily visual stimulation by gratings of different spatial frequencies and contrast reduces tumor growth. The effects of sensory input are region-specific, as visual deprivation has no significant effect on tumor proliferation in mice with gliomas in the motor cortex. We also report that sensory stimulation combined with temozolomide administration delays the loss of visual responses in peritumoral neurons. Altogether, these data demonstrate complex effects of different neuronal subtypes in the control of glioma proliferation. |
| first_indexed | 2024-12-17T00:39:46Z |
| format | Article |
| id | doaj.art-d2d0bd48dbbc47d88a91d898da1ce1f5 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T00:39:46Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d2d0bd48dbbc47d88a91d898da1ce1f52022-12-21T22:10:03ZengElsevierNeurobiology of Disease1095-953X2020-07-01141104942Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferationElena Tantillo0Eleonora Vannini1Chiara Cerri2Cristina Spalletti3Antonella Colistra4Chiara Maria Mazzanti5Mario Costa6Matteo Caleo7Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy; Fondazione Pisana per la Scienza Onlus (FPS), via Ferruccio Giovannini 13, San Giuliano Terme, 56017 Pisa, Italy; Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100 Pisa, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy; Fondazione Umberto Veronesi, Piazza Velasca 5, 20122 Milan, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy; Fondazione Umberto Veronesi, Piazza Velasca 5, 20122 Milan, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, ItalyFondazione Pisana per la Scienza Onlus (FPS), via Ferruccio Giovannini 13, San Giuliano Terme, 56017 Pisa, ItalyNeuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy; Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100 Pisa, Italy; Corresponding authors at: Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy.Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy; Department of Biomedical Sciences, University of Padua, via G. Colombo 3, 35121 Padua, Italy; Corresponding authors at: Neuroscience Institute, National Research Council (CNR), via G. Moruzzi 1, 56124 Pisa, Italy.Recent studies have demonstrated an active role for neurons in glioma progression. Specifically, peritumoral neurons establish functional excitatory synapses with glioma cells, and optogenetic stimulation of cortical pyramidal neurons drives tumor progression. However, the specific role of different subsets of cortical neurons, such as GABAergic interneurons, remains unexplored. Here, we directly compared the effects of optogenetic stimulation of pyramidal cells vs. fast-spiking, GABAergic neurons. In mice inoculated with GL261 cells into the motor cortex, we show that optogenetic stimulation of pyramidal neurons enhances glioma cell proliferation. In contrast, optogenetic stimulation of fast-spiking, parvalbumin-positive interneurons reduces proliferation as measured by BrdU incorporation and Ki67 immunolabelling. Since both principal cells and fast-spiking interneurons are directly activated by sensory afferent input, we next placed tumors in the occipital cortex to test the impact of visual stimulation/deprivation. We report that total lack of visual input via dark rearing enhances the density of proliferating glioma cells, while daily visual stimulation by gratings of different spatial frequencies and contrast reduces tumor growth. The effects of sensory input are region-specific, as visual deprivation has no significant effect on tumor proliferation in mice with gliomas in the motor cortex. We also report that sensory stimulation combined with temozolomide administration delays the loss of visual responses in peritumoral neurons. Altogether, these data demonstrate complex effects of different neuronal subtypes in the control of glioma proliferation.http://www.sciencedirect.com/science/article/pii/S0969996120302175Parvalbumin-positive interneuronsGABAGlioma cell proliferationAfferent sensory input |
| spellingShingle | Elena Tantillo Eleonora Vannini Chiara Cerri Cristina Spalletti Antonella Colistra Chiara Maria Mazzanti Mario Costa Matteo Caleo Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation Neurobiology of Disease Parvalbumin-positive interneurons GABA Glioma cell proliferation Afferent sensory input |
| title | Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation |
| title_full | Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation |
| title_fullStr | Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation |
| title_full_unstemmed | Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation |
| title_short | Differential roles of pyramidal and fast-spiking, GABAergic neurons in the control of glioma cell proliferation |
| title_sort | differential roles of pyramidal and fast spiking gabaergic neurons in the control of glioma cell proliferation |
| topic | Parvalbumin-positive interneurons GABA Glioma cell proliferation Afferent sensory input |
| url | http://www.sciencedirect.com/science/article/pii/S0969996120302175 |
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