Umbelliferone Ameliorates Memory Impairment and Enhances Hippocampal Synaptic Plasticity in Scopolamine-Induced Rat Model

• Published in: Nutrients 2023-05, Vol.15 (10), p.2351
• Main Authors: Choi, Ga-Young, Kim, Hyun-Bum, Cho, Jae-Min, Sreelatha, Inturu, Lee, In-Seo, Kweon, Hee-Seok, Sul, Sehyun, Kim, Sun Ae, Maeng, Sungho, Park, Ji-Ho
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholinesterase; Acetylcholinesterase - metabolism; Advertising executives; Alzheimer Disease - metabolism; Alzheimer's disease; Animal cognition; Animals; Antidiabetics; Brain slice preparation; Brain-derived neurotrophic factor; Cholinergics; Cognitive ability; Cyclic AMP response element-binding protein; Diabetes mellitus; Glutamic acid receptors (ionotropic); Hippocampus; Hippocampus - metabolism; Immunological memory; Impairment; Inflammation; Information storage; Kinases; Laboratory animals; Learning; Long-term potentiation; Male; Memory; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - metabolism; N-Methyl-D-aspartic acid receptors; Nervous system; Nervous system diseases; Neuronal Plasticity; Neuroprotection; Parkinson's disease; Rats; Rats, Sprague-Dawley; Reagents; Scopolamine; Scopolamine - adverse effects; Scopolamine - metabolism; Signs and symptoms; Synaptic density; Tissue analysis; TrkB receptors; Ultrastructure; umbelliferone; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15102351

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.