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

Abstract

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.

Nöropeptid W, kronik stresli sıçanlarda bilişsel bozukluğu ve kaygı benzeri davranışları hafifletir

“…36 The increased expression of BDNF, TrkB, the pCREB/CREB ratio, and the inhibition of acetylcholinesterase activity were associated with cognitive improvements. 37 It was reported that about the interrelationships between BDNF and NPW, BDNF could modulate the expression of NPW in neuronal cells via the PI3K/Akt pathway and the application of exogenous BDNF to mice increased synthesis of NPW and also CRH levels in the hypothalamus. 38 NPW participates in the neuroendocrine regulation of pituitary hormone production and may have a significant role in the hypothalamic organization of the endocrine response to stress.…”