Enhancement of Striatal Dopaminergic Function Following Autologous Neural Cell Ecosystems (ANCE) Transplantation in a Non-Human Primate Model of Parkinson’s Disease

Borgognon, Simon; Cottet, Jérôme; Moret, Véronique; Chatagny, Pauline; Ginovart, Nathalie; Antonescu, Cristian; Bloch, Jocelyne; Brunet, Jean‐François; Rouiller, Eric M.; Badoud, Simon

doi:10.4172/2161-0460.1000383

Cited by 7 publications

(60 citation statements)

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“…d Percentage decrease with reference to 18F‐Dopa uptake in striatum prelesion. It means that 18F‐Dopa uptake reincreased post‐ANCE transplantation as compared to post‐MPTP lesion, as recently reported (Borgognon et al., ). e Lesion volume in Mk‐AG could not be determined due to a few missing histological sections.…”

Section: Methodssupporting

confidence: 75%

“… In MPTP monkeys, the percentage of functional recovery (“recov”) or improvement (“impr”) was assessed based on the Schneider score (Sch‐s), the time spent in freezing activity (fr‐a) and the traveled distance (dist). The percentage of improvement was measured by comparing the median values post‐ANCE implantation versus the post‐MPTP lesion (time window before ANCE; see Borgognon et al., ): less time in freezing activity, more distance travelled. Manual dexterity data in MPTP monkeys will be published later.…”

Section: Resultsmentioning

confidence: 99%

“…(). Information about dopaminergic neuronal loss in SNpc, as well as about decrease of 18 F‐DOPA uptake in the striatum (post‐MPTP lesion and post‐ANCE transplantation), is available in Table (see also Borgognon et al., ).…”

Section: Methodsmentioning

confidence: 99%

“…Parkinson's disease animals were treated with autologous neural cell ecosystems (ANCE: see Borgognon et al., ) obtained by cell culture of cortical neurons developed in vitro from cortical biopsies (Table ). The protocol for cortical biopsy surgery was the same as that previously published (Badoud et al., ), whereas the protocols to prepare the cell culture and cell labelling were the same as previously used (Bloch et al., ; Brunet et al., , ).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were implanted via a Hamilton microsyringe (10 μl culture medium; 2 μl/min during 5 min per injection site) using a nanoinjector (Stoelting, Wood Dale, IL, USA) fixed to a stereotaxic frame. Each animal received between 250,000 and 400,000 cells (Borgognon et al., ).…”

Section: Methodsmentioning

confidence: 99%

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Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys

Fregosi

Contestabile

Badoud

et al. 2018

Eur J of Neuroscience

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Functional recovery from central nervous system injury is likely to be partly due to a rearrangement of neural circuits. In this context, the corticobulbar (corticoreticular) motor projections onto different nuclei of the ponto‐medullary reticular formation (PMRF) were investigated in 13 adult macaque monkeys after either, primary motor cortex injury (MCI) in the hand area, or spinal cord injury (SCI) or Parkinson's disease‐like lesions of the nigro‐striatal dopaminergic system (PD). A subgroup of animals in both MCI and SCI groups was treated with neurite growth promoting anti‐Nogo‐A antibodies, whereas all PD animals were treated with autologous neural cell ecosystems (ANCE). The anterograde tracer BDA was injected either in the premotor cortex (PM) or in the primary motor cortex (M1) to label and quantify corticobulbar axonal boutons terminaux and en passant in PMRF. As compared to intact animals, after MCI the density of corticobulbar projections from PM was strongly reduced but maintained their laterality dominance (ipsilateral), both in the presence or absence of anti‐Nogo‐A antibody treatment. In contrast, the density of corticobulbar projections from M1 was increased following opposite hemi‐section of the cervical cord (at C7 level) and anti‐Nogo‐A antibody treatment, with maintenance of contralateral laterality bias. In PD monkeys, the density of corticobulbar projections from PM was strongly reduced, as well as that from M1, but to a lesser extent. In conclusion, the densities of corticobulbar projections from PM or M1 were affected in a variable manner, depending on the type of lesion/pathology and the treatment aimed to enhance functional recovery.

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Section: Methodssupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys

Fregosi

Contestabile

Badoud

et al. 2018

Eur J of Neuroscience

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Loss of motor cortical inputs to the red nucleus after central nervous system disorders in non-human primates

Borgognon

Rouiller

2022

Preprint

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The premotor (PM) and primary motor (M1) cortical areas broadcast voluntary motor commands through multiple neuronal pathways, including the corticorubral projection that reaches the red nucleus (RN). However, the respective contribution of M1 and PM to corticorubral projections as well as its plasticity following motor disorders or injuries are not known in non-human primates. Here, we quantified the density and topography of axonal endings of the corticorubral pathway in RN in intact monkeys, as well as in monkeys subjected to either cervical spinal cord injury (SCI), Parkinson's disease (PD)-like symptoms or primary motor cortex injury (MCI). Twenty adult macaque monkeys were injected with the biotinylated dextran amine (BDA) anterograde tracer either in PM or in M1. We developed a semi-automated algorithm to reliably detect and count axonal boutons within the magnocellular (mRN) and parvocellular (pRN) subdivisions of RN. In intact monkeys, PM and M1 preferentially target the medial part of the ipsilateral pRN, reflecting its somatotopic organization. PM's projection to the ipsilateral pRN is denser than M1's, matching previous observations for the corticotectal, corticoreticular, and corticosubthalamic projections (Fregosi et al., 2018, 2019; Borgognon et al., 2020). In all three types of motor disorders, there was a uniform and strong decrease (near loss) of the corticorubral projections from PM and M1. The RN may contribute to functional recovery after SCI, PD and MCI, by reducing direct cortical influence. This reduction possibly privileges direct access to the final output motor system, via emphasis on the direct corticospinal projection.

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Fine Manual Dexterity Assessment After Autologous Neural Cell Ecosystem (ANCE) Transplantation in a Non-human Primate Model of Parkinson’s Disease

Borgognon

Cottet

Moret

et al. 2019

Neurorehabil Neural Repair

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Background. Autologous neural cell ecosystem (ANCE) transplantation improves motor recovery in MPTP monkeys. These motor symptoms were assessed using semi-quantitative clinical rating scales, widely used in many studies. However, limitations in terms of sensitivity, combined with relatively subjective assessment of their different items, make inter-study comparisons difficult to achieve. Objective. The aim of this study was to quantify the impact of MPTP intoxication in macaque monkeys on manual dexterity and assess whether ANCE can contribute to functional recovery. Methods. Four animals were trained to perform 2 manual dexterity tasks. After reaching a motor performance plateau, the animals were subjected to an MPTP lesion. After the occurrence of a spontaneous functional recovery plateau, all 4 animals were subjected to ANCE transplantation. Results. Two of 4 animals underwent a full spontaneous recovery before the ANCE transplantation, whereas the 2 other animals (symptomatic) presented moderate to severe Parkinson’s disease (PD)-like symptoms affecting manual dexterity. The time to grasp small objects using the precision grip increased in these 2 animals. After ANCE transplantation, the 2 symptomatic animals underwent a significant functional recovery, reflected by a decrease in time to execute the different tasks, as compared with the post-lesion phase. Conclusions. Manual dexterity is affected in symptomatic MPTP monkeys. The 2 manual dexterity tasks reported here as pilot are pertinent to quantify PD symptoms and reliably assess a treatment in MPTP monkeys, such as the present ANCE transplantation, to be confirmed in a larger cohort of animals before future clinical applications.

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Enhancement of Striatal Dopaminergic Function Following Autologous Neural Cell Ecosystems (ANCE) Transplantation in a Non-Human Primate Model of Parkinson’s Disease

Cited by 7 publications

References 59 publications

Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys

Changes of motor corticobulbar projections following different lesion types affecting the central nervous system in adult macaque monkeys

Loss of motor cortical inputs to the red nucleus after central nervous system disorders in non-human primates

Fine Manual Dexterity Assessment After Autologous Neural Cell Ecosystem (ANCE) Transplantation in a Non-human Primate Model of Parkinson’s Disease

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