Scabronine G Methyl Ester Improves Memory-Related Behavior and Enhances Hippocampal Cell Proliferation and Long-Term Potentiation via the BDNF-CREB Pathway in Olfactory Bulbectomized Mice

被引：16

作者：

Nakagawasai, Osamu ^{[1
]}

Lin, Jia-Rong ^{[1
]}

Odaira, Takayo ^{[1
]}

Takahashi, Kohei ^{[1
,2
]}

Nemoto, Wataru ^{[1
]}

Moriguchi, Shigeki ^{[3
,4
]}

Yabuki, Yasushi ^{[4
,5
]}

Kobayakawa, Yu ^{[6
]}

Fukunaga, Kohji ^{[4
]}

Nakada, Masahisa ^{[6
]}

Tan-No, Koichi ^{[1
]}

机构：

[1] Tohoku Med & Pharmaceut Univ, Fac Pharmaceut Sci, Dept Pharmacol, Sendai, Miyagi, Japan

[2] Int Univ Hlth & Welf, Sch Pharm, Dept Pharmacol, Ohtawara, Japan

[3] Tohoku Univ, Grad Sch Pharmaceut Sci, Res Ctr Pharmaceut Dev, Sendai, Miyagi, Japan

[4] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sendai, Miyagi, Japan

[5] Kumamoto Univ, Inst Mol Embryol & Genet, Dept Genom Neurol, Kumamoto, Japan

[6] Waseda Univ, Dept Chem & Biochem, Fac Sci & Engn, Tokyo, Japan

来源：

FRONTIERS IN PHARMACOLOGY | 2020年 / 11卷

关键词：

long-term potentiation; memory; olfactory bulbectomy; scabronine G methyl ester; cell proliferation; CAM KINASE-II; NEUROTROPHIC FACTOR; DENTATE GYRUS; COGNITIVE IMPAIRMENT; ANTIDEPRESSANT DRUGS; NEUROGENESIS; RAT; ACTIVATION; RECEPTOR; MODEL;

D O I：

10.3389/fphar.2020.583291

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A previous study reported that scabronine G methyl ester (SG-ME) potentially enhances the in vitro secretion of neurotrophic factors such as nerve growth factor via the protein kinase C (PKC)-zeta pathway. However, it remains unknown whether SG-ME can improve cognitive dysfunctions in olfactory bulbectomized (OBX) mice. To address this question, we evaluated SG-ME-treated and untreated OBX mice in a passive avoidance test. We also investigated potential effects of SG-ME on several parameters: cell proliferation and cAMP response element-binding protein (CREB) phosphorylation in the hippocampal dentate gyrus by immunohistochemistry, brain-derived neurotrophic factor (BDNF) levels in the hippocampus by Western blotting, p-CREB levels in the hippocampus by MapAnalyzer, and long-term potentiation (LTP) by electrophysiology. On the 14th day after surgery OBX mice showed altered passive avoidance and decreases in both cell proliferation and long-term potentiation in the hippocampus, while these changes were reversed by SG-ME (20 mu g/mouse) 24 h after the treatment. The improvement in memory deficits was prevented when SG-ME was co-administeredwith either zeta inhibitory peptide (PKC-zeta inhibitor), anti-BDNF antibody, ANA-12 (TrkB antagonist), U0126 (MEK inhibitor), H-89 (PKA inhibitor), LY294002 (PI3K inhibitor) or KN-93 (CaMKII inhibitor). We found that SG-ME enhanced brain-derived neurotrophic factor and p-CREB levels in the hippocampus while p-CREB was localized in neurons, but not in astrocytes nor microglial cells. These findings revealed the potential of SG-ME in improving memory impairments by enhancing cell proliferation and LTP via activation of the BDNF/CREB signaling pathway in neurons.

引用

页数：13