The Novel Cognitive Enhancer ST101 Enhances Acetylcholine Release in Mouse Dorsal Hippocampus Through T-type Voltage-Gated Calcium Channel Stimulation

DOI Web Site Web Site PubMed 19 Citations 75 References
  • Yamamoto Yui
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
  • Shioda Norifumi
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
  • Han Feng
    Institute of Pharmacology and Toxicology and Biochemical Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, China
  • Moriguchi Shigeki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
  • Fukunaga Kohji
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan

Bibliographic Information

Other Title
  • Novel cognitive enhancer ST101 enhances acetylcholine release in mouse dorsal hippocampus through T-type voltage-gated calcium channel stimulation

Search this article

Abstract

We recently developed a novel cognitive enhancer, ST101 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one), that activates T-type voltage-gated calcium channels (VGCCs). Here, we address whether T-type VGCC activation with ST101 mediates its cognitive effects in vivo and the relevance of T-type VGCC activation to acetylcholine (ACh) release in the hippocampus. Acute intraperitoneal administration of ST101 (1 mg/kg, i.p.) improved memory-related behaviors in both olfactory bulbectomized (OBX) and scopolamine-treated mice. Effects of ST101 administration were abolished by both intraperitoneal and intracerebroventricular pre-administration of the T-type VGCC inhibitor mibefradil. Acute administration of ST101 enhanced basal and nicotine-induced ACh release in the dorsal hippocampus in both OBX and sham-treated mice. Enhanced ACh release was abolished by infusion with mibefradil (10 μM) but not with the L-type VGCC inhibitor nifedipine (10 μM). As expected, significantly reduced CaMKIIα, PKCα, and ERK phosphorylation was restored by acute ST101 administration in the OBX mouse hippocampal CA1 region. Enhancement of CaMKIIα and PKCα but not ERK phosphorylation was inhibited by mibefradil (20 mg/kg, i.p.) preadministration. Increased CaMKIIα and PKCα phosphorylation was confirmed by increased phosphorylation of GluR1, synapsin I, and NR1. Taken together, stimulation of T-type VGCCs is critical for the enhanced hippocampal ACh release and improved cognitive function seen following ST101 administration.

Journal

Citations (19)*help

See more

References(75)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top