Screening inducers of neuronal BDNF gene transcription using primary cortical cell cultures from BDNF-luciferase transgenic mice.

Abstract

Brain-derived neurotrophic factor (BDNF) is a key player in synaptic plasticity, and consequently, learning and memory. Because of its fundamental role in numerous neurological functions in the central nervous system, BDNF has utility as a biomarker and drug target for neurodegenerative and neuropsychiatric disorders. Here, we generated a screening assay to mine inducers of Bdnf transcription in neuronal cells, using primary cultures of cortical cells prepared from a transgenic mouse strain, specifically, Bdnf-Luciferase transgenic (Bdnf-Luc) mice. We identified several active extracts from a library consisting of 120 herbal extracts. In particular, we focused on an active extract prepared from Ginseng Radix (GIN), and found that GIN activated endogenous Bdnf expression via cAMP-response element-binding protein-dependent transcription. Taken together, our current screening assay can be used for validating herbal extracts, food-derived agents, and chemical compounds for their ability to induce Bdnf expression in neurons. This method will be beneficial for screening of candidate drugs for ameliorating symptoms of neurological diseases associated with reduced Bdnf expression in the brain, as well as candidate inhibitors of aging-related cognitive decline.

• Authors: Mamoru Fukuchi, Yui Okuno, Hironori Nakayama, Aoi Nakano, Hisashi Mori, Satoru Mitazaki, Yuka Nakano, Kazufumi Toume, Michiko Jo, Ichiro Takasaki, Kazuki Watanabe, Naotoshi Shibahara, Katsuko Komatsu, Akiko Tabuchi, Masaaki Tsuda
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 11833 (08 14 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31413298 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Brain-Derived Neurotrophic Factor
• Cyclic AMP Response Element-Binding Protein
• Ginsenosides
• Plant Extracts
• Receptors, Lysophosphatidic Acid
• gintonin
• Luciferases
• Dopamine

Topics

• Animals
• Brain-Derived Neurotrophic Factor (genetics, metabolism)
• Cells, Cultured
• Cerebral Cortex (cytology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Dopamine (metabolism)
• Ginsenosides (pharmacology)
• Luciferases (metabolism)
• Mass Screening
• Mice, Transgenic
• Neurons (drug effects, metabolism)
• Plant Extracts (pharmacology)
• Rats, Sprague-Dawley
• Receptors, Lysophosphatidic Acid (metabolism)
• Signal Transduction
• Transcription, Genetic (drug effects)