Melatonin Improves Cognitive Deficits via Restoration of Cholinergic Dysfunction in a Mouse Model of Scopolamine-Induced Amnesia

Abstract

Melatonin is known to improve cognitive deficits, and its functions have been studied in various disease models, including Alzheimer's disease. In this study, we investigated effects of melatonin on cognition and the cholinergic system of the septum and hippocampus in a mouse model of scopolamine-induced amnesia. Scopolamine (1 mg/kg) and melatonin (10 mg/kg) were administered intraperitoneally to mice for 2 and 4 weeks. The Morris water maze and passive avoidance tests revealed that both treatments of scopolamine significantly impaired spatial learning and memory; however, 2- and 4-week melatonin treatments significantly improved spatial learning and memory. In addition, scopolamine treatments significantly decreased protein levels and immunoreactivities of choline acetyltransferase (ChAT), high-affinity choline transporter (CHT), vesicular acetylcholine transporter (VAChT), and muscarinic acetylcholine receptor M1 (M1R) in the septum and hippocampus. However, the treatments with melatonin resulted in increased ChAT-, CHT-, VAChT-, and M1R-immunoreactivities and their protein levels in the septum and hippocampus. Our results demonstrate that melatonin treatment is effective in improving the cognitive deficits via restoration of the cholinergic system in the septum and hippocampus of a mouse model of scopolamine-induced amnesia.

Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

“…After deacetylation of Ach by cholinesterase in the synaptic space, choline reuptake into presynaptic terminals is performed by a high-affinity choline transporter (CHT1) 34 . Treatment with melatonin and N -acetyl-5-methoxytryptamine has been shown to inhibit the reduction of the levels of the proteins ChAT, VAchT, CHT1, and M1-mAchRs and improve the cognitive deficit in scopolamine-induced amnesia 35 . NGF also increases VAchT as well as ChAT and CHT1 via the Akt/PKB signaling pathway 36 .…”

Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients

“…The results revealed that melatonin increased acetylcholinesterase (AChE) levels as well as BDNF/CREB1 protein expression levels in the prefrontal cortex of mice and improved recognition memory and passive avoidance performance. Chen et al (2018) found that intraperitoneal injection of scopolamine in mice significantly reduced the protein levels and immunoreactivity of ChAT, high-affinity choline transporter (CHT), vesicle acetylcholine Preventive melatonin attenuated isoflurane-induced cognitive impairment and its effects were depended on the hippocampal MT2-CREB signaling pathway.…”

Protective effect of ginsenoside Rh2 on scopolamine‐induced memory deficits through regulation of cholinergic transmission, oxidative stress and the ERK‐CREB‐BDNF signaling pathway

“…Researchers have developed a scopolamine (Scop)‐induced amnesia model, which is useful for investigating the progression of AD. The model mainly manifests cholinergic transmission dysfunction in the central nervous system (Chen et al, 2018). Furthermore, there is increasing evidence that Scop interferes with the molecular homeostasis of extracellular signal‐regulated kinase (ERK) and cAMP response element binding (CREB)/brain derived neurotrophic factor (BDNF) in animal models (Corpuz, Fujii, Nakamura, & Katayama, 2019; Ko, Kwon, Lee, & Jang, 2017), while simulating ERK/CREB/BDNF injury in the brains of patients with AD (Diniz & Teixeira, 2011; Saura & Valero, 2011).…”