Neurogenesis continues to occur in restricted areas of the postnatal and adult brain, and is modulated by environmental stimuli. Newly generated neurons in the adult brain can propagate action potentials and are synaptically connected. The origin of these neurons and the lineage potential of neural progenitor cells found in the adult brain are still poorly understood. In this proposal we will use a transgenic mouse line expressing enhanced green fluorescent protein (EGFP) under the control of the myelin gene promoter 2'-3' cyclic nucleotide 3-phosphodiesterase (CNP). We have recently found that CNP-EGFP+ progenitor cells expressing the chondroitin proteoglycan NG2 and isolated from the postnatal brain of these mice can generate neurons, oligodendrocytes and astrocytes. By using a multidisciplinary cellular, molecular and electrophysiological approach, we will determine whether the lineage and cell specification potential of perinatal NG2+/CNP-EGFP+ cells is conserved throughout postnatal development and in the adult brain in vitro and in vivo. We will define the identity of neurons generated from perinatal and adult NG2+/CNP-EGFP+ progenitor cells. Because of their well-established involvement in neural cell specification during development, we will also study the role of Notch receptor pathways in the differentiation of postnatal NG2+/CNP-EGFP+ cells to neurons. We have also accumulated experimental evidence indicating that, in the hippocampus in vivo, NG2+/CNP-EGFP+ cells can generate new glutamate decarboxylase+ (GAD+), dlx+ GABAergic neurons throughout the entire postnatal period into adulthood. We will characterize these EGFP+ neurons by using anatomical, electrophysiological and imunocytochemical approaches. By analyzing their electrophysiological properties, including their integration into synaptic circuits, we will assess their functional development. Finally, we will determine if these differentiated neurons display synaptic plasticity in the hippocampus during development. Together these studies will not only provide new insights into adult neurogenesis, but will also help design strategies to induce neuronal repair by triggering generation of new neurons from a selected population of endogenous glial-neuronal progenitors.
| Morton, Paul D; Korotcova, Ludmila; Lewis, Bobbi K et al. (2017) Abnormal neurogenesis and cortical growth in congenital heart disease. Sci Transl Med 9: |
| Penn, Anna A; Gressens, Pierre; Fleiss, Bobbi et al. (2016) Controversies in preterm brain injury. Neurobiol Dis 92:90-101 |
| Agematsu, Kota; Korotcova, Ludmila; Morton, Paul D et al. (2016) Hypoxia diminishes the protective function of white-matter astrocytes in the developing brain. J Thorac Cardiovasc Surg 151:265-72.e1-3 |
| Jablonska, Beata; Gierdalski, Marcin; Chew, Li-Jin et al. (2016) Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury. Nat Commun 7:13866 |
| Morton, Paul D; Ishibashi, Nobuyuki; Jonas, Richard A et al. (2015) Congenital cardiac anomalies and white matter injury. Trends Neurosci 38:353-63 |
| Dimou, L; Gallo, V (2015) NG2-glia and their functions in the central nervous system. Glia 63:1429-51 |
| Zonouzi, Marzieh; Scafidi, Joseph; Li, Peijun et al. (2015) GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury. Nat Neurosci 18:674-82 |
| Agematsu, Kota; Korotcova, Ludmila; Scafidi, Joseph et al. (2014) Effects of preoperative hypoxia on white matter injury associated with cardiopulmonary bypass in a rodent hypoxic and brain slice model. Pediatr Res 75:618-25 |
| Salmaso, Natalina; Jablonska, Beata; Scafidi, Joseph et al. (2014) Neurobiology of premature brain injury. Nat Neurosci 17:341-6 |
| Hammond, Timothy R; Gadea, Ana; Dupree, Jeff et al. (2014) Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron 81:588-602 |
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