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Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration.
Neurotoxicology 2019; 76:153-161N

Abstract

Parkinson's disease (PD) is characterized by profound microglial driven inflammatory processes and the loss of dopamine neurons of the substantia nigra (SNc). Both microglia and dopamine neurons that are affected in the SNc are particularly vulnerable to environmental toxicants and finding more selective ways of targeting these cell types is of importance. Quantum dots (QDs) might be a useful vehicle for selectively delivering toxicants to microglia and owing to their fluorescent capability, they can be microscopically tracked within the cell. Accordingly, we assessed the impact of QDs alone and QDs conjugated to the ribosomal toxin, saporin, upon SNc microglia and dopamine neurons. We found that intra-SNc infused QDs selectively entered microglia and induced morphological changes consistent with an activated state. QDs conjugated to saporin also caused a significant loss of dopamine neurons and motor coordination (on a rotarod test) deficits, along with an increase in the inflammatory microglial actin regulatory factors, WAVE2. These data suggest that QDs might be a viable route for toxicant delivery and also has an added advantage of being fluorescently visible. Ultimately, we found SNc neurons to be exceptionally vulnerable to QD-saporin and suggest that this could be a novel targeted approach to model PD-like inflammatory pathology.

Authors+Show Affiliations

Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada.Department of Neuroscience, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6, Canada. Electronic address: shawn_hayley@carleton.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31738977

Citation

Landrigan, Jeffery, et al. "Quantum Dot Conjugated Saporin Activates Microglia and Induces Selective Substantia Nigra Degeneration." Neurotoxicology, vol. 76, 2019, pp. 153-161.
Landrigan J, Dwyer Z, Beauchamp S, et al. Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration. Neurotoxicology. 2019;76:153-161.
Landrigan, J., Dwyer, Z., Beauchamp, S., Rodriguez, R., Fortin, T., & Hayley, S. (2019). Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration. Neurotoxicology, 76, pp. 153-161. doi:10.1016/j.neuro.2019.11.007.
Landrigan J, et al. Quantum Dot Conjugated Saporin Activates Microglia and Induces Selective Substantia Nigra Degeneration. Neurotoxicology. 2019 Nov 15;76:153-161. PubMed PMID: 31738977.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantum dot conjugated saporin activates microglia and induces selective substantia nigra degeneration. AU - Landrigan,Jeffery, AU - Dwyer,Zach, AU - Beauchamp,Sheryl, AU - Rodriguez,Ruth, AU - Fortin,Teresa, AU - Hayley,Shawn, Y1 - 2019/11/15/ PY - 2019/02/19/received PY - 2019/11/01/revised PY - 2019/11/14/accepted PY - 2019/11/19/pubmed PY - 2019/11/19/medline PY - 2019/11/19/entrez KW - Dopamine KW - Microglia KW - Quantum dot KW - Saporin KW - Toxicant SP - 153 EP - 161 JF - Neurotoxicology JO - Neurotoxicology VL - 76 N2 - Parkinson's disease (PD) is characterized by profound microglial driven inflammatory processes and the loss of dopamine neurons of the substantia nigra (SNc). Both microglia and dopamine neurons that are affected in the SNc are particularly vulnerable to environmental toxicants and finding more selective ways of targeting these cell types is of importance. Quantum dots (QDs) might be a useful vehicle for selectively delivering toxicants to microglia and owing to their fluorescent capability, they can be microscopically tracked within the cell. Accordingly, we assessed the impact of QDs alone and QDs conjugated to the ribosomal toxin, saporin, upon SNc microglia and dopamine neurons. We found that intra-SNc infused QDs selectively entered microglia and induced morphological changes consistent with an activated state. QDs conjugated to saporin also caused a significant loss of dopamine neurons and motor coordination (on a rotarod test) deficits, along with an increase in the inflammatory microglial actin regulatory factors, WAVE2. These data suggest that QDs might be a viable route for toxicant delivery and also has an added advantage of being fluorescently visible. Ultimately, we found SNc neurons to be exceptionally vulnerable to QD-saporin and suggest that this could be a novel targeted approach to model PD-like inflammatory pathology. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/31738977/Quantum_dot_conjugated_saporin_activates_microglia_and_induces_selective_substantia_nigra_degeneration L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(19)30134-2 DB - PRIME DP - Unbound Medicine ER -