Recovery from experimental parkinsonism by intrastriatal application of erythropoietin or EPO-releasing neural precursors

Carelli, Stephana; Giallongo, Toniella; Viaggi, Cristina; Latorre, Elisa; Gombalová, Zuzana Tonelli; Raspa, Andrea; Mazza, M.; Vaglini, Francesca; Giulio, Anna Maria Di; Gorio, Alfredo

doi:10.1016/j.neuropharm.2017.03.035

Cited by 19 publications

(68 citation statements)

References 73 publications

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“…We previously reported that Er-NPCs release erythropoietin ( Marfia et al, 2011 ), and their intrastriatal injection promoted recovery of function in a model of Parkinson’s disease through erythropoietin release ( Carelli et al, 2016 ; Carelli et al, 2017 ). After i.v.…”

Section: Discussionmentioning

confidence: 99%

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

Carelli

Giallongo

Gombalová

et al. 2017

RNN

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Background:Spinal cord injury (SCI) is a debilitating condition characterized by a complex of neurological dysfunctions ranging from loss of sensation to partial or complete limb paralysis. Recently, we reported that intravenous administration of neural precursors physiologically releasing erythropoietin (namely Er-NPCs) enhances functional recovery in animals following contusive spinal cord injury through the counteraction of secondary degeneration. Er-NPCs reached and accumulated at the lesion edges, where they survived throughout the prolonged period of observation and differentiated mostly into cholinergic neuron-like cells.Objective:The aim of this study was to investigate the potential reparative and regenerative properties of Er-NPCs in a mouse experimental model of traumatic spinal cord injury.Methods and Results:We report that Er-NPCs favoured the preservation of axonal myelin and strongly promoted the regrowth across the lesion site of monoaminergic and chatecolaminergic fibers that reached the distal portions of the injured cord. The use of an anterograde tracer transported by the regenerating axons allowed us to assess the extent of such a process. We show that axonal fluoro-ruby labelling was practically absent in saline-treated mice, while it resulted very significant in Er-NPCs transplanted animals.Conclusion:Our study shows that Er-NPCs promoted recovery of function after spinal cord injury, and that this is accompanied by preservation of myelination and strong re-innervation of the distal cord. Thus, regenerated axons may have contributed to the enhanced recovery of function after SCI.

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Section: Discussionmentioning

confidence: 99%

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

Carelli

Giallongo

Gombalová

et al. 2017

RNN

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“…Neural stem cells (NSCs) are multipotent stem cells present in the central nervous system (CNS) with self-renewing capabilities and the ability to generate all the main cellular phenotypes present in the nervous system, including neurons, astrocytes and oligodendrocytes [1]. NSCs were first observed as resident progenitors in the sub-ventricular zone (SVZ) and dentate gyrus of the mouse brain [2], and have later found a strong use in regenerative medicine [3][4][5][6][7][8][9]. In that context, NSCs are described to act both by releasing anti-inflammatory soluble factors and by differentiating into cellular components of the CNS [4][5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…NSCs were first observed as resident progenitors in the sub-ventricular zone (SVZ) and dentate gyrus of the mouse brain [2], and have later found a strong use in regenerative medicine [3][4][5][6][7][8][9]. In that context, NSCs are described to act both by releasing anti-inflammatory soluble factors and by differentiating into cellular components of the CNS [4][5][6][7][8][9][10][11][12]. Many progresses have been made in understanding the factors that regulate adult NSCs' specification, proliferation and differentiation, but much remains to be understood, especially the potential involvement of RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) in these processes [13].…”

Section: Introductionmentioning

confidence: 99%

HuR interacts with lincBRN1a and lincBRN1b during neuronal stem cells differentiation

et al. 2019

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LncRNAs play crucial roles in cellular processes and their regulatory effects in the adult brain and neural stem cells (NSCs) remain to be entirely characterized. We report that 10 lncRNAs (LincENC1, FABL, lincp21, HAUNT, PERIL, lincBRN1a, lincBRN1b, HOTTIP, TUG1 and FENDRR) are expressed during murine NSCs differentiation and interact with the RNA-binding protein ELAVL1/HuR. Furthermore, we characterize the function of two of the deregulated lncRNAs, lincBRN1a and lincBRN1b, during NSCs' differentiation. Their inhibition leads to the induction of differentiation, with a concomitant decrease in stemness and an increase in neuronal markers, indicating that they exert key functions in neuronal cells differentiation. Furthermore, we describe here that HuR regulates their half-life, suggesting their synergic role in the differentiation process. We also identify six human homologs (PANTR1, TUG1, HOTTIP, TP53COR, ELDRR and FENDRR) of the mentioned 10 lncRNAs and we report their deregulation during human iPSCs differentiation into neurons. In conclusion, our results strongly indicate a key synergic role for lncRNAs and HuR in neuronal stem cells fate.

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“…EPO has protective and treating effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neurotoxicity in this mouse model of Parkinson's Disease via increasing nitric oxide production [5,6]. In addition, Carelli et al [47] study shows that EPO, whether ectopically administered or released by neural precursors, does reverse MPTP-induced Parkinsonism in mice. Unilateral stereotaxic injection of erythropoietin-releasing neural precursor cells can rescue degenerating striatal DA neurons and promote behavioral recovery [47].…”

Section: Introductionmentioning

confidence: 92%

“…In addition, Carelli et al [47] study shows that EPO, whether ectopically administered or released by neural precursors, does reverse MPTP-induced Parkinsonism in mice. Unilateral stereotaxic injection of erythropoietin-releasing neural precursor cells can rescue degenerating striatal DA neurons and promote behavioral recovery [47]. Recently, two studies in humans have investigated safety and efficacy of EPO treatment of PD patients.…”

Section: Introductionmentioning

confidence: 98%

Point of View about Erythropoietin in Treatment of Central Nervous System Diseases

Yang¹,

Li²,

Wu³

et al. 2017

J Alzheimers Dis Parkinsonism

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Recovery from experimental parkinsonism by intrastriatal application of erythropoietin or EPO-releasing neural precursors

Cited by 19 publications

References 73 publications

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

HuR interacts with lincBRN1a and lincBRN1b during neuronal stem cells differentiation

Point of View about Erythropoietin in Treatment of Central Nervous System Diseases

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