Ginkgo biloba extract increases neurite outgrowth and activates the Akt/mTOR pathway

English version

Autoři: Imane Lejri ^aff001; Amandine Grimm ^aff001; Anne Eckert ^aff001
Působiště autorů: University of Basel, Neurobiology Lab for Brain Aging and Mental Health, Transfaculty Research Platform Molecular and Cognitive Neuroscience, Basel, Switzerland ^aff001; Psychiatric University Clinics, University of Basel, Basel, Switzerland ^aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225761

Souhrn

Background

Standardized Ginkgo biloba extract (GBE) has demonstrated efficacy in the cognitive functional neuropsychiatric symptoms of patients with Alzheimer’s disease (AD). With regard to its underlying molecular mode of action, first evidence was provided that GBE was able to modulate neuronal outgrowth in vitro, but the mechanisms underlying GBE effects on neuroplasticity remain unclear.

Methodology/Principal findings

In this study, we investigated the effect of GBE on neurite outgrowth using SH-SY5Y neuroblastoma cells in a 2D and 3D surface culture. The effects of the GBE LI1370 on neuroplasticity and neurite outgrowth were compared to those of nerve growth factor (NGF, 50 ng/ml) which was used as a positive control. We evaluated several parameters of neurite outgrowth such as the neurite number, total neurite length and extend of branching. Our findings showed that GBE (10 and 100 μg/ml) significantly increased neurite outgrowth in the 2D as well as 3D culture model after 3 days of treatment with a comparable effect than that NGF. The use of the 3D cell culture allowed us to better reproduce the in vivo neuronal microenvironment for the evaluation the neurite formation after GBE treatment. In addition, we assessed the effects of GBE on the Akt/mTOR pathway, which is known to promote neuroplasticity induced by nerve growth factors. We showed that GBE treatment induced an increase of phosphorylated IGF1R (Tyr1135/Tyr1136), Akt (Ser473), TSC2 (Ser939), mTOR (Ser2448), PTEN (Ser380) and GSK3β (Ser9).

Conclusion

Together, these findings indicate that GBE promotes neurite growth and activates the PI3K/Akt/mTOR pathway suggesting that this plant extract supports neuronal plasticity.

Klíčová slova:

Cell cultures – Mitochondria – Phosphorylation – Confocal microscopy – Neurites – Neuronal plasticity – Neuroblastoma cells – Nerve growth factor

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