Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways

• Published in: Journal of ethnopharmacology 2017-03, Vol.200, p.16-21
• Main Authors: Jo, So Yeon, Jung, In Ho, Yi, Jee Hyun, Choi, Tae Joon, Lee, Seungheon, Jung, Ji Wook, Yun, Jeanho, Lee, Young Choon, Ryu, Jong Hoon, Kim, Dong Hyun
• Format: Article
• Language: English
• Subjects: A mitogen-activated protein kinase; Adenylyl cyclase; Adenylyl Cyclases - metabolism; Animals; Cyclic AMP-Dependent Protein Kinases - metabolism; Ethanol - pharmacology; Hippocampus - drug effects; Hippocampus - physiology; Male; Mice; Mitogen-Activated Protein Kinases - metabolism; Organ Culture Techniques; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Protein kinase A; Seeds; Signal Transduction - drug effects; Signal Transduction - physiology; Synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Ziziphus; Zizyphus jujuba var. spinose; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2017.02.009

As the seed of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) has been used to sleep disturbances in traditional Chinese and Korean medicine, many previous studies have focused on its sedative effect. Recently, we reported the neuroprotective effect of the effect of Z. jujuba var. spinosa. However, its effects on synaptic function have not yet been studied. In this project, we examined the action of ethanol extract of the seed of Z. jujuba var. spinosa (DHP1401) on synaptic transmission in the hippocampus. To investigate the effects of DHP1401, field recordings were conducted using hippocampal slices (400µm). Object recognition test was introduced to examine whether DHP1401 affect normal recognition memory. DHP1401 (50μg/ml) induced a significant increase in synaptic activity in Shaffer collateral pathway in a concentration-dependent manner. This increase of synaptic responses was blocked by NBQX, a broad spectrum α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, but not IEM-1460, a Ca2+-permeable AMPAR blocker. Moreover, U0126, a mitogen-activated protein kinase inhibitor, SQ22536, an adenylyl cyclase inhibitor, and PKI, a protein kinase A inhibitor, blocked DHP1401-induced increase in synaptic transmission. Finally, DHP1401 facilitated object recognition memory. These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK. [Display omitted]