1. NGF, TrkA-P and neuroprotection after a hypoxic event in the developing central nervous system
- Author
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Melina Rapacioli, Victorio Martin Pozo Devoto, Sara Fiszer de Plazas, María Eugenia Bogetti, and Vladimir Flores
- Subjects
0301 basic medicine ,Central Nervous System ,Embryo, Nonmammalian ,Time Factors ,NEUROTROPHIN ,Apoptosis ,Chick Embryo ,Tropomyosin receptor kinase A ,purl.org/becyt/ford/1 [https] ,0302 clinical medicine ,Nerve Growth Factor ,Hypoxia ,Cells, Cultured ,Neurons ,NEUROPROTECTION ,biology ,Cell Death ,Biología del Desarrollo ,Age Factors ,Cell Hypoxia ,Neuroprotection ,medicine.anatomical_structure ,ACUTE HYPOXIA ,medicine.symptom ,CIENCIAS NATURALES Y EXACTAS ,Neurotrophin ,medicine.medical_specialty ,Programmed cell death ,Superior Colliculi ,Central nervous system ,CELL DEATH ,Ciencias Biológicas ,03 medical and health sciences ,Developmental Neuroscience ,Internal medicine ,medicine ,In Situ Nick-End Labeling ,Animals ,Receptor, trkA ,purl.org/becyt/ford/1.6 [https] ,OPTIC TECTUM ,Hypoxia (medical) ,030104 developmental biology ,Endocrinology ,Nerve growth factor ,nervous system ,biology.protein ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
A decrease in the concentration of oxygen in the blood and tissues (hypoxia) produces important, sometimes irreversible, damages in the central nervous system (CNS) both during development and also postnatally. The present work aims at analyzing the expression of nerve growth factor (NGF) and p75 and the activation of TrkA in response to an acute normobaric hypoxic event and to evaluate the possible protective role of exogenous NGF. The developing chick optic tectum (OT), a recognized model of corticogenesis, was used as experimental system by means of in vivo and in vitro studies. Based on identification of the period of highest sensitivity of developmental programmed cell death (ED15) we show that hypoxia has a mild but reproducible effect that consist of a temporal increase of cell death 6 h after the end of a hypoxic treatment. Cell death was preceded by a significant early increase in the expression of Nerve Growth Factor (NGF) and its membrane receptor p75. In addition, we found a biphasic response of TrkA activation: a decrease during hypoxia followed by an increase −4 h later- that temporally coincide with the interval of NGF overexpression. To test the NGF - NGF receptors role in hypoxic cell death, we quantified, in primary neuronal cultures derived from ED15 OT, the levels of TrkA activation after an acute hypoxic treatment. A significant decline in the level of TrkA activation was observed during hypoxia followed, 24 h later, by significant cell death. Interestingly, this cell death can be reverted if TrkA inactivation during hypoxia is suppressed by the addition of NGF. Our results suggest that TrkA activation may play an important role in the survival of OT neurons subjected to acute hypoxia. The role of TrkA in neuronal survival after injury may be advantageously used for the generation of neuroprotective strategies to improve prenatal insult outcomes. Fil: Bogetti, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Pozo Devoto, Victorio Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Rapacioli, Melina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina Fil: Flores, Domingo Vladimir. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Neurociencia Cognitiva. Fundación Favaloro. Instituto de Neurociencia Cognitiva; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Fiszer de Plazas, Sara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina
- Published
- 2018
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