Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine and N-docosahexaenoyl dopamine examined in neuronal precursors derived from human pluripotent stem cells

Abstract

Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1–10 μM range. However, both agents at 10 μM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.

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Abbreviations

CB1(2):

cannabinoid receptor type 1(2)

DHDA:

N-docosahexaenoyl dopamine

ECs:

endocannabinoids

ECS:

endocannabinoid system

iPSCs:

induced pluripotent stem cells

MTT (assay):

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (assay)

NADA:

N-arachidonoyl dopamine

ROS:

reactive oxygen species

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Correspondence to E. V. Novosadova or I. A. Grivennikov.

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Original Russian Text © E. V. Novosadova, E. L. Arsenyeva, E. S. Manuilova, L. G. Khaspekov, M. Yu. Bobrov, V. V. Bezuglov, S. N. Illarioshkin, I. A. Grivennikov, 2017, published in Biokhimiya, 2017, Vol. 82, No. 11, pp. 1732–1739.

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Novosadova, E.V., Arsenyeva, E.L., Manuilova, E.S. et al. Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine and N-docosahexaenoyl dopamine examined in neuronal precursors derived from human pluripotent stem cells. Biochemistry Moscow 82, 1367–1372 (2017). https://doi.org/10.1134/S0006297917110141

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Keywords

  • endocannabinoids
  • N-arachidonoyl dopamine
  • N-docosahexaenoyl dopamine
  • neuroprotection
  • induced pluripotent stem cells
  • neural precursors
  • oxidative stress