Neuroprotective and neurotoxic effects of endocannabinoid-like compounds, N-arachidonoyl dopamine and N-docosahexaenoyl dopamine in differentiated cultures of induced pluripotent stem cells derived from patients with Parkinson’s disease

Influence of N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine on the Expression of Neurotrophic Factors in Neuronal Differentiated Cultures of Human Induced Pluripotent Stem Cells under Conditions of Oxidative Stress

“…Earlier, we determined the sensitivity of neuronal cells to H 2 O 2 and showed that, when using 200 µM of H 2 O 2 , approximately 50% of β-III-tubulin positive cells die [ 11 ]. In this way 200 µM H 2 O 2 was used to induce OS in the investigated cultures.…”

“…Recently, we have shown that N-ADA and N-DDA exert neuroprotective effects in the cultures of neuronal progenitors differentiated from human induced pluripotent stem cells (iPSC) obtained from a healthy donor in the model of OS induced by hydrogen peroxide [ 10 ]. Further experiments performed on neuronal progenitors and cultures of terminally differentiated neurons enriched with dopaminergic (DA) neurons obtained from iPSC of healthy donors, as well as from patients with Parkinson’s disease, confirmed the neuroprotective effect of these compounds in the same model of OS [ 11 ]. Moreover, the protective effect of N-ADA and N-DDA was not associated with their interaction with hydrogen peroxide.…”

“…Moreover, the protective effect of N-ADA and N-DDA was not associated with their interaction with hydrogen peroxide. It was suggested that neuroprotective and antioxidant effects of these compounds could be mediated through the induction of expression of a number of neurotrophic and antiapoptotic factors in these cells [ 11 ]. It is well known that neurotrophic factors (NTFs) play a key role in the development, differentiation, synaptogenesis and survival of brain neurons and in the processes of their adaptation to external influences, including acute or chronic stress [ 12 ].…”

Transcriptome datasets of neural progenitors and neurons differentiated from induced pluripotent stem cells of healthy donors and Parkinson's disease patients with mutations in the PARK2 gene

“…iPSC cultures generated from somatic cells of healthy and PD donors [ 13 , 14 ] were maintained in hPSC XF Medium (Sartorius, Germany). To start iPSC differentiation in neuronal direction [15] the culture medium was replaced with medium for NPs (DMEM/F12 medium supplemented with 2% serum replacement (Gibco, USA) and a mix of factors: 1 mM non-essential amino acids (Paneco, Russian Federation), 2 mM L -glutamine (ICN Biomedicals Inc, USA), penicillin-streptomycin(50 U/ml; 50 µg/ml) (Paneco, Russian Federation), 1% N2 supplement (Life Technologies, USA), 10 µM SB431542 (Stemgent, USA), and 80 ng recombinant Noggin (Peprotech, USA)). After 10–14 days of culturing, neural rosettes with specific “ridges” were formed.…”

Novel Approaches Used to Examine and Control Neurogenesis in Parkinson′s Disease

“…Particularly, the generation of neurons and glial cells from a patient became possible, thereby allowing the reconstruction of key processes of brain plasticity, development of brain tissue in vitro models, and establishment of isogenic platforms for cell-replacement therapy and cell transplantation [68]. As we have shown before, such an approach was effective in the generation of PD-derived iPSC lines with different mutations for studying defects in neurotrophic factors signaling affecting neuronal development [19], personalized modeling of PD pathogenesis [69], and screening of drug candidates [70,71]. The optimized protocols for getting dopaminergic differentiated neurons from iPSCs have been suggested [72,73], and they include the recruitment of stem cells with the transforming growth factor-beta (TGFβ) antagonists, activation of Hedgehog, Wnt, and fibroblast growth factor 8 (FGF8) signaling pathways or expression of Lmx1a, Foxa2, and Nurr1 and other midbrain-specific transcription factors for getting the midbrain floor-plate progenitors, followed by the application of neurotrophic factors (brain-derived neurotrophic factor BDNF, glia cell line-derived neurotrophic factor GDNF) and Notch receptor antagonists to induce the terminal differentiation of cells toward a dopaminergic phenotype.…”