title: Acute rosmarinic acid treatment enhances long-term potentiation, BDNF and GluR-2 protein expression, and cell survival rate against scopolamine challenge in rat organotypic hippocampal slice cultures.
abstract: Rosmarinic acid (RA) is a polyphenolic ester of caffeic acid and is commonly found in the Nepetoideae subfamily of flowering mint plants. Because RA has previously exhibited antioxidant, neuroprotective, and antidepressant-like effects, we evaluated its influences on cellular functions in neuronal cultures.
  
  
  
  To elucidate possible mechanisms of RA, we investigated the influences of acute RA administration on long-term potentiation (LTP), plasticity-related protein expression, and scopolamine-induced cell death in organotypic hippocampal slice cultures.
  
  
  
  LTP analysis in organotypic hippocampal slice cultures (OHSCs) was carried out with various ion channel blockers, such as AP5 (10 μM), CNQX (10 μM), niflumic acid (100 μM), and scopolamine (300 μM) in response to RA (1, 10 or 100 μg/mL) treatment. Protein expression and cell death assays in the presence of scopolamine were examined to observe the effects of RA. For LTP analysis, baseline field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1 by a 60-channel multielectrode array (MEA) every min for 40 min before 15 min of high-frequency stimulation (HFS) to the Schaffer collaterals and commissural pathways, followed by a successive 50 min of recording. For protein expression measurements, anti-BDNF and anti-GluR2 antibodies were used for Western blotting assays in whole-hippocampal tissue homogenate. Finally, for cell death assays, OHSCs were exposed to a culture medium containing propidium iodide (PI) for 24 or 48 h, followed by the assessment of cell death by fluorescent image analysis of PI uptake.
  
  
  
  and discussion: Our results indicate that RA treatment enhances fEPSPs following HFS in CA1 synapses at 1 and 10 μg/ml RA, an effect that was inhibited by CNQX and NFA but not by AP5. RA treatment also increases the expression of BDNF and GluR-2 proteins and prevents cell death of scopolamine-exposed OHSCs. Our results suggest the possibility that rosmarinic acid can enhance neural plasticity by modulating glutamatergic signaling pathways, as well as providing neuroprotection with reduced cholinergic activity.
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
authors.forename: Eun-Sang
authors.initials: ES
authors.lastname: Hwang
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
authors.forename: Hyun-Bum
authors.initials: HB
authors.lastname: Kim
authors.affiliation: Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin 446-701, Republic of Korea.
authors.forename: Ga-Young
authors.initials: GY
authors.lastname: Choi
authors.affiliation: Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Oriental Medicinal Materials and Processing, College of Life Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, 446-701, Republic of Korea.
authors.forename: Sung-Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sannok-go, Ansan, Gyenggi-do, 15588, Republic of Korea. Electronic address: talpiot@hanyang.ac.kr.
authors.forename: SangSeong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of East-West Medicine, Graduate School of East-West Medical Science, Kyung Hee University, Deogyeong-daero, Giheung-gu, Yongin 446-701, Republic of Korea. Electronic address: jihopark@khu.ac.kr.
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism*; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D002934:Cinnamates; D053630:Depsides; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D000097123:Rosmarinic Acid; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Hippocampus; Long-term potentiation (LTP); Multielectrode array (MEA); Neuronal plasticity; Neuroprotection; Rosmarinic acid (RA)