THE GLIAL RECEPTOR MECHANISM OF THE SYNTHESIS AND RELEASE OF BRAIN-DERIVED NEUROTROPHIC FACTOR WHEN EXPOSED TO PROGESTERONE IS MEDIATED VIA THE CLASSICAL PROGESTERONE RECEPTOR

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2014-03

Authors

Lee, Jay J.
Su, Chang
Singh, Meharvan

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Abstract

Purpose (a): Progesterone (P4) is cytoprotective in various experimental models, but our understanding of the mechanisms involved is still incomplete. It has been implicated that brain-derived neurotrophic factor (BDNF) signaling is an important mediator of P4’s protective actions. This experiment looked into a potential receptor mechanism by which progesterone can mediate BDNF synthesis, which is via the classical progesterone receptor (PR). C6 glial cells are neuronal cells that normally lack classical PR, and so it is an ideal model to look at the classical PR response to progesterone with relation to BDNF. The hypothesis is that cells that have the classical PR will synthesize more BDNF relative to cells that do not have the classical PR. Methods (b): In this experiment, a set of C6 glial cell cultures were transfected with classical PR genes. After allowing for growth, both the transfected and non-transfected C6 cells were exposed to progesterone and the concentration of BDNF in the cell lysis was determined via ELISA. Results (c): The results revealed that for the C6 cells that were not transfected with the classical PR, there was no significant change in the level of BDNF release regardless of the progesterone treatment (vehicle, 30 pg/mL BDNF; 0.1 nM P4, 29 pg/mL BDNF; 1 nM P4, 29 pg/mL BDNF; 10 nM P4, 31 pg/mL BDNF; 100 nM P4, 30 pg/mL BDNF; 1000 nM P4, 29 pg/mL BDNF). On the other hand, the C6 cells that were transfected with the classical PR showed an increase in BDNF production with the treatment of progesterone. The transfected C6 cells that were not treated with progesterone but rather with vehicle DMSO showed a BDNF release of 37 pg/mL. The transfected C6 cells that were treated with progesterone at concentrations of 10 nM and 100 nM showed a BDNF release of 61 pg/mL and 50 pg/mL respectively (P < 0.01). Conclusions (d): Overall, these results show that one receptor mechanism in neuronal cells that results in BDNF synthesis is via the classical progesterone receptor. The presence of the classical PR in C6 glial cells resulted in a statistically significant difference in the synthesis of BDNF relative to those that lack PR. Identifying and elucidating the mechanism by which progesterone confers neuroprotective benefits may aid in the development of new or novel treatments and/or drugs aimed at the prevention or treatment of many neurodegenerative diseases such as Alzheimer’s disease.

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