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

VL - 43

SP - 86

EP - 98

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1

ER -