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Neuroprotective Properties of Endocannabinoids N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine Examined in Neuronal Precursors Derived from Human Pluripotent Stem Cells

E. V. Novosadova1*, E. L. Arsenyeva1, E. S. Manuilova1, L. G. Khaspekov2, M. Yu. Bobrov3,4, V. V. Bezuglov3, S. N. Illarioshkin2, and I. A. Grivennikov1*

1Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia; E-mail: novek-img@mail.ru, grivigan@mail.ru

2Research Center of Neurology, 125367 Moscow, Russia

3Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

4Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 117997 Moscow, Russia

* To whom correspondence should be addressed.

Received August 3, 2017; Revision received August 23, 2017
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.
KEY WORDS: endocannabinoids, N-arachidonoyl dopamine, N-docosahexaenoyl dopamine, neuroprotection, induced pluripotent stem cells, neural precursors, oxidative stress

DOI: 10.1134/S0006297917110141