The 6‐hydroxydopamine‐induced nigrostriatal neurodegeneration produces microglia‐like NG2 glial cells in the rat substantia nigra

Kitamura, Yoshihisa; Inden, Masatoshi; Minamino, Hideaki; Abe, Mari; Takata, Kazuyuki; Taniguchi, Takashi

doi:10.1002/glia.21040

Cited by 45 publications

(47 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dose of LPS and 6-OHDA was chosen based on previous published data. 15,27,29,49,50 Control animals of the same age were injected with PBS. The amount of SC001 injected was calculated taking into account the distribution volume of this cerebral area and the effective dose observed in the in vitro experiments.…”

Section: ■ Methodsmentioning

confidence: 99%

Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.

Morales-García

Susín

Alonso‐Gil

et al. 2012

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by degeneration of the nigrostriatal dopaminergic pathway. Because the current therapies only lead to temporary, limited improvement and have severe side effects, new approaches to treat PD need to be developed. To discover new targets for potential therapeutic intervention, a chemical genetic approach involving the use of small molecules as pharmacological tools has been implemented. First, a screening of an in-house chemical library on a wellestablished cellular model of PD was done followed by a detailed pharmacological analysis of the hits. Here, we report the results found for the small heterocyclic derivative called SC001, which after different enzymatic assays was revealed to be a new glycogen synthase kinase-3 (GSK-3) inhibitor with IC 50 = 3.38 ± 0.08 μM. To confirm that GSK-3 could be a good target for PD, the evaluation of a set of structurally diverse GSK-3 inhibitors as neuroprotective agents for PD was performed. Results show that inhibitors of GSK-3 have neuroprotective effects in vitro representing a new pharmacological option for the disease-modifying treatment of PD. Furthermore, we show that SC001 is able to cross the blood−brain barrier, protects dopaminergic neurons, and reduces microglia activation in in vivo models of Parkinson disease, being a good candidate for further drug development.

show abstract

Section: ■ Methodsmentioning

confidence: 99%

Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.

Morales-García

Susín

Alonso‐Gil

et al. 2012

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In a study examining two rat models of PD, NG2—positive cells expressed calcium-binding adaptor molecule 1 and GDNF. (118) It has also been seen that subcutaneous injection of a cytokine mixture containing granulocyte macrophage colony-stimulating factor and interleukin-3 ameliorated loss of dopaminergic neurons in one of these rat PD models. One possible mechanism for this reduction of degradation is thought to be the increase in NG2—positive glia found in treated animals.…”

Section: Gags In Neurological Disordersmentioning

confidence: 97%

“…One possible mechanism for this reduction of degradation is thought to be the increase in NG2—positive glia found in treated animals. (118, 119) Hence NG2-positive glia seems important for the survival of dopaminergic neurons and presents NG2 as a possible therapeutic target for PD.…”

Section: Gags In Neurological Disordersmentioning

confidence: 99%

Sugar glues for broken neurons

Swarup¹,

Hlady

Kuberan³

2013

BioMolecular Concepts

View full text Add to dashboard Cite

Proteoglycans regulate diverse functions in the CNS by interacting with a number of growth factors, matrix proteins and cell surface molecules. Heparan sulfate and chondroitin sulfate are two major glycosaminoglycans present in the PGs of CNS. Functionality of these PGs is to a large extent dictated by the fine sulfation patterns present on their GAG chains. In the past 15 years, there has been a significant expansion in our knowledge on the role of HS and CS chains in various neurological processes such as neuronal growth, regeneration, plasticity and pathfinding. However, defining the relationship between distinct sulfation patterns of the GAGs and their functionality has so far been difficult. With the emergence of novel tools for synthesis of defined GAG structures, and techniques for their characterization, we are now in a better position to explore the structure—function relationship of GAGs in the context of their sulfation patterns. In this review, we discuss the importance GAGs on CNS development, injury and disorders with an emphasis on their sulfation patterns. Finally, we outline several GAG based therapeutic strategies to exploit GAG chains for ameliorating various CNS disorders.

show abstract

“…Oligodendrocyte and NG2 + derived factors have been postulated to play a neurotrophic/neuroprotective role for dopaminergic neurons [19,20]. On the other hand, disturbances in nigral oligodendrogenesis seem to be pathognomonic in PD brain [21,22].…”

Section: Introductionmentioning

confidence: 99%

Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra in a dopamine-dependent manner

et al. 2012

View full text Add to dashboard Cite

BackgroundParkinson’s disease is characterized by a continuous loss of neurons within the substantia nigra (SN) leading to a depletion of dopamine. Within the adult SN as a non-neurogenic region, cells with mainly oligodendrocytic precursor characteristics, expressing the neuro-glial antigen-2 (NG2) are continuously generated. Proliferation of these cells is altered in animal models of Parkinson’s disease (PD). Exercise and environmental enrichment re-increase proliferation of NG2+ cells in PD models, however, a possible mechanistic role of dopamine for this increase is not completely understood. NG2+ cells can differentiate into oligodendrocytes but also into microglia and neurons as observed in vitro suggesting a possible hint for endogenous regenerative capacity of the SN. We investigated the role of dopamine in NG2-generation and differentiation in the adult SN stimulated by physical activity and environmental enrichment.ResultsWe used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model for dopamine depletion and analysed newborn cells in the SN at different maturation stages and time points depending on voluntary physical activity, enriched environment and levodopa-treatment. We describe an activity- induced increase of new NG2-positive cells and also mature oligodendrocytes in the SN of healthy mice. Running and enriched environment refused to stimulate NG2-generation and oligodendrogenesis in MPTP-mice, an effect which could be reversed by pharmacological levodopa-induced rescue.ConclusionWe suggest dopamine being a key regulator for activity-induced generation of NG2-cells and oliogodendrocytes in the SN as a potentially relevant mechanism in endogenous nigral cellular plasticity.

show abstract

The 6‐hydroxydopamine‐induced nigrostriatal neurodegeneration produces microglia‐like NG2 glial cells in the rat substantia nigra

Cited by 45 publications

References 50 publications

Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.

Glycogen Synthase Kinase-3 Inhibitors as Potent Therapeutic Agents for the Treatment of Parkinson Disease.

Sugar glues for broken neurons

Physical activity and environmental enrichment regulate the generation of neural precursors in the adult mouse substantia nigra in a dopamine-dependent manner

Contact Info

Product

Resources

About