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RCSN Cell System for Identifying Dopaminergic Neurotoxicity

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Handbook of Neurotoxicity

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Abstract

Dopaminergic toxicity represents a potential mechanism underlying Parkinson’s disease (PD) neuropathology. Nevertheless, the study of such a mechanism is hampered by the lack of permanent and stable in vitro models that bear relevant cellular traits, namely, neuronal dopaminergic function. Although various permanent cell lines exhibiting variable dopaminergic properties do exist, such properties are not necessarily stable and may require the application of complex and costly differentiation protocols for induction. The latter is particularly true when inducing in vitro differentiation from more undifferentiated tissue, such as stem cells. Also, cell lines may lose viability or eventually undergo permanent differentiation. This chapter discusses a permanently growing cell line, named RCSN-3, which was established from the substantia nigra of an adult Fisher 344 rat. The cell line retains dopaminergic traits, including dopamine production and secretion, and the presence of catecholamine reuptake transporters. Notably, these properties have remained expressed in RCSN-3 cells for decades. This chapter also addresses the contribution of RCSN-3 to dopaminergic-mediated toxic phenomena, in particular, and to the identification of potential therapeutical targets in dopaminergic neurons. Finally, RCSN-3 cells are also presented as a model for cell transplant therapy, in animal models of PD, and their contribution in this field is discussed in relation to more recently available cell sources, such as stem cells and induced pluripotent stem cells (iPSCs).

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Abbreviations

GABA:

Gamma-aminobutyric acid

HPLC:

High-performance liquid chromatography

iPSCs:

Induced pluripotent stem cells

LRRK2:

Leucine-rich repeat kinase 2

MAP-2:

Microtubule associated protein-2

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NSE:

Neuron specific enolase

PD:

Parkinson’s disease

PINK1:

PTEN-induced putative kinase 1

PTEN:

Phosphatase and tensin homolog deleted on chromosome 10

ROS:

Reactive oxygen species

SN:

Substantia nigra

SNCA:

Alpha-synuclein gene

TH:

Tyrosine hydroxilase

MPP+:

1-Methyl-4-phenylpyridinium.

DAT:

Dopamine transporter

NET:

Norepinephrine transporter

VMAT-2:

Vesicular monoamine transporter-2

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Conflict of Interest

Dr. Pablo Caviedes declares intellectual property protection on the RCSN-3 cell line (Freeman et al., 2012) and the cell culture clustering protocol depicted in Fig. 2 (Caviedes et al., 2012).

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Authors and Affiliations

  1. Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile

    Pablo Caviedes, Raúl Caviedes & Juan Segura-Aguilar

  2. Centre for Biotechnology & Bioengineering (CeBiB), Department of Chemical Engineering, Biotechnology & Materials, Faculty of Physical & Mathematical Sciences, University of Chile, Santiago, Chile

    Pablo Caviedes

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  1. Pablo Caviedes
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  2. Raúl Caviedes
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Correspondence to Pablo Caviedes .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Caviedes, P., Caviedes, R., Segura-Aguilar, J. (2021). RCSN Cell System for Identifying Dopaminergic Neurotoxicity. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_56-1

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