TY - JOUR
T1 - Adult neural precursors isolated from post mortem brain yield mostly neurons
T2 - An erythropoietin-dependent process
AU - Marfia, Giovanni
AU - Madaschi, Laura
AU - Marra, Francesca
AU - Menarini, Mauro
AU - Bottai, Daniele
AU - Formenti, Alessandro
AU - Bellardita, Carmelo
AU - Di Giulio, Anna Maria
AU - Carelli, Stephana
AU - Gorio, Alfredo
PY - 2011/7
Y1 - 2011/7
N2 - This study was aimed at the isolation of neural precursor cells (NPCs) capable of resisting to a prolonged ischemic insult as this may occur at the site of traumatic and ischemic CNS injuries. Adult mice were anesthetized and then killed by cervical dislocation. The cadavers were maintained at room temperature or at 4. °C for different time periods. Post mortem neural precursors (PM-NPCs) were isolated, grown in vitro and their differentiation capability was investigated by evaluating the expression of different neuronal markers. PM-NPCs differentiate mostly in neurons, show activation of hypoxia-inducible factor-1 and MAPK, and express both erythropoietin (EPO) and its receptor (EPO-R). The exposure of PM-NPCs to neutralizing antibodies to EPO or EPO-R dramatically reduced the extent of neuronal differentiation to about 11% of total PM-NPCs. The functionality of mTOR and MAPK is also required for the expression of the neuronal phenotype by PM-NPCs. These results suggest that PM-NPCs can be isolated from animal cadaver even several hours after death and their self-renewable capability is comparable to normal neural precursors. Differently, their ability to achieve a neural phenotype is superior to that of NPCs, and this is mediated by the activation of hypoxia-induced factor 1 and EPO signaling. PM-NPCs may represent good candidates for transplantation studies in animal models of neurodegenerative diseases.
AB - This study was aimed at the isolation of neural precursor cells (NPCs) capable of resisting to a prolonged ischemic insult as this may occur at the site of traumatic and ischemic CNS injuries. Adult mice were anesthetized and then killed by cervical dislocation. The cadavers were maintained at room temperature or at 4. °C for different time periods. Post mortem neural precursors (PM-NPCs) were isolated, grown in vitro and their differentiation capability was investigated by evaluating the expression of different neuronal markers. PM-NPCs differentiate mostly in neurons, show activation of hypoxia-inducible factor-1 and MAPK, and express both erythropoietin (EPO) and its receptor (EPO-R). The exposure of PM-NPCs to neutralizing antibodies to EPO or EPO-R dramatically reduced the extent of neuronal differentiation to about 11% of total PM-NPCs. The functionality of mTOR and MAPK is also required for the expression of the neuronal phenotype by PM-NPCs. These results suggest that PM-NPCs can be isolated from animal cadaver even several hours after death and their self-renewable capability is comparable to normal neural precursors. Differently, their ability to achieve a neural phenotype is superior to that of NPCs, and this is mediated by the activation of hypoxia-induced factor 1 and EPO signaling. PM-NPCs may represent good candidates for transplantation studies in animal models of neurodegenerative diseases.
KW - Adult neural progenitors
KW - Erythropoietin
KW - Gene regulation
KW - Hypoxia- inducible factor-1 (HIF-1)
KW - MTOR
KW - Neural plasticity
UR - http://www.scopus.com/inward/record.url?scp=79955946493&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2011.02.004
DO - 10.1016/j.nbd.2011.02.004
M3 - Journal article
C2 - 21324364
AN - SCOPUS:79955946493
SN - 0969-9961
VL - 43
SP - 86
EP - 98
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1
ER -