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Exp Neurobiol 2019; 28(2): 158-171

Published online April 30, 2019

https://doi.org/10.5607/en.2019.28.2.158

© The Korean Society for Brain and Neural Sciences

Extracellular Vesicles Derived from Lactobacillus plantarum Increase BDNF Expression in Cultured Hippocampal Neurons and Produce Antidepressant-like Effects in Mice

Juli Choi1, Yoon-Keun Kim2, and Pyung-Lim Han1,3*

1Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul 03760, Korea.

2MD Healthcare Inc., Seoul 03923, Korea.

3Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3277-4130, FAX: 82-2-3277-3419
e-mail: plhan@ewha.ac.kr

Received: September 22, 2018; Revised: March 25, 2019; Accepted: March 28, 2019

Gut microbiota play a role in regulating mental disorders, but the mechanism by which gut microbiota regulate brain function remains unclear. Gram negative and positive gut bacteria release membrane-derived extracellular vesicles (EVs), which function in microbiota-host intercellular communication. In the present study, we investigated whether Lactobacillus plantarum derived EVs (L-EVs) could have a role in regulating neuronal function and stress-induced depressive-like behaviors. HT22 cells treated with the stress hormone glucocorticoid (GC; corticosterone) had reduced expression of Bdnf and Sirt1, whereas L-EV treatment reversed GC-induced decreased expression of Bdnf and Sirt1. The siRNA-mediated knockdown of Sirt1 in HT22 cells decreased Bdnf4, a splicing variant of Bdnf, and Creb expression, suggesting that Sirt1 plays a role in L-EV-induced increase of BDNF and CREB expression. Mice exposed to restraint for 2-h daily for 14 days (CRST) exhibited depressive-like behaviors, and these CRST-treated mice had reduced expression of Bdnf and Nt4/5 in the hippocampus. In contrast, L-EV injection prior to each restraint treatment blocked the reduced expression of Bdnf and Nt4/5, and stress-induced depressive-like behaviors. Furthermore, L-EV treatment in CRST-treated mice also rescued the reduced expression of Bdnf, and blocked stress-induced depressive-like behaviors. These results suggest that Lactobacillus derived EVs can change the expression of neurotropic factors in the hippocampus and afford antidepressant-like effects in mice with stress-induced depression.

Graphical Abstract


Keywords: Extracellular vesicles, Lactobacillus plantarum, BDNF, Antidepressant-like effects