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.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These results suggest that DHP1401 increase synaptic transmission through increase of synaptic AMPAR transmission via MAPK, AC and PAK.
Department of Biotechnology, College of Natural Resources and Life Science, Dong-A University, Busan 49315, Republic of Korea. Electronic address: csy2863@gmail.com.
So Yeon
SY
Jo
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 02447, Republic of Korea; Daehwa Pharmaceutical Co., Ltd., Seongnam 13488, Republic of Korea. Electronic address: inhojung69@gmail.com.
In Ho
IH
Jung
School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK. Electronic address: JeeHyun.Yi@bristol.ac.uk.
Jee Hyun
JH
Yi
Daehwa Pharmaceutical Co., Ltd., Seongnam 13488, Republic of Korea. Electronic address: cjswoid@gmail.com.
Tae Joon
TJ
Choi
Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: slee76@jejunu.ac.kr.
Seungheon
S
Lee
Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University, Kyungsan 38610, Republic of Korea. Electronic address: jwjung@dhu.ac.kr.
Ji Wook
JW
Jung
Department of Biochemistry, College of Medicine, Dong-A University, Busan 607-714, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: yunj@dau.ac.kr.
Jeanho
J
Yun
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: yclee@dau.ac.kr.
Young Choon
YC
Lee
Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 02447, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jhryu63@khu.ac.kr.
Jong Hoon
JH
Ryu
Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Republic of Korea; Institute of Convergence Bio-Health, Dong-A University, Busan 49315, Republic of Korea. Electronic address: mose79@dau.ac.kr.
Dong Hyun
DH
Kim
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009924:Organ Culture Techniques; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D031957:Ziziphus
D010936:Plant Extracts; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases
A mitogen-activated protein kinase; Adenylyl cyclase; Protein kinase A; Synaptic transmission; Zizyphus jujuba var. spinose; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor