Acetylcholine bidirectionally regulates learning and memory

Huang, Qinhong; Liao, Canming; Ge, Fan; Ao, Jian; Liu, Ting

doi:10.1016/j.jnrt.2022.100002

Cited by 53 publications

(17 citation statements)

References 284 publications

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“…Further, AChE activity and ACh levels were estimated in the brain homogenate (Figure B, C). ACh binds to nicotinic and muscarinic receptors, which are involved in memory and learning . Treatment with PD07 significantly lowered the AChE activity in rats in a dose-dependent manner as compared to DPZ.…”

Section: Resultsmentioning

confidence: 99%

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Bhanukiran

Singh

et al. 2023

ACS Chem. Neurosci.

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The naturally inspired multitarget-directed ligands (PC01–PC10 and PD01–PD26) were synthesized from piperine for the management of Alzheimer’s disease (AD). The compound PD07 showed significant inhibitory activity on ChEs, BACE1, and Aβ1–42 aggregation in in vitro studies. Further, compound PD07 effectively displaced the propidium iodide at the AChE PAS site. The compound PD07 exhibited significant lipophilicity in PAMPA studies. Additionally, PD07 demonstrated neuroprotective properties in the Aβ1–42 induced SH-SY5Y cell line. Furthermore, DFT calculations were performed using B3LYP/6-311G(d,p) basis sets to explore the PD07 physical and chemical properties. The compound PD07 showed a similar binding interaction profile at active sites of AChE, BuChE, and BACE1 proteins as compared to reference ligands (donepezil, tacrine, and BSD) in molecular docking and dynamic simulation studies. In acute oral toxicity studies, compound PD07 exhibited no toxicity symptoms up to 300 mg/kg, po. The compound PD07 (10 mg/kg, po) improved memory and cognition in scopolamine-induced amnesia rats. Further, PD07 increased ACh levels in the brain by inhibiting the AChE activity. The results from in vitro, in silico, and in vivo studies suggested that compound PD07 is a potent multitarget-directed lead from piperine to overcome Alzheimer’s disease.

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Section: Resultsmentioning

confidence: 99%

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Bhanukiran

Singh

et al. 2023

ACS Chem. Neurosci.

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“…Although this discrepancy is not clearly understood, low acetylcholine is reportedly associated with non-motor symptoms of PD [ 61 ]. Moreover, the advanced stage of PD is associated with concurrent loss of dopamine and acetylcholine [ 62 ]. Interestingly, ribose-cysteine and levodopa monotherapy and combined therapy protected against the α-Syn-induced disruption of neurotransmitter activities.…”

Section: Discussionmentioning

confidence: 99%

Ribose-cysteine and levodopa abrogate Parkinsonism via the regulation of neurochemical and redox activities in alpha-synuclein transgenic Drosophila melanogaster models

Idowu,

Oremosu,

Dosumu

et al. 2024

Fly

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Parkinson’s disease (PD), the most prevalent type of parkinsonism, is a progressive neurodegenerative condition marked by several non-motor and motor symptoms. PD is thought to have a complex aetiology that includes a combination of age, genetic predisposition, and environmental factors. Increased expression of α-synuclein (α-Syn) protein is central to the evolvement of neuropathology in this devastating disorder, but the potential of ribose-cysteine and levodopa in abating pathophysiologic changes in PD model is unknown. Crosses were set up between flies conditionally expressing a pathological variant of human α-Syn (UAS-α-Syn) and those expressing GAL4 in neurons (elav-GAL4) to generate offspring referred to as PD flies. Flies were randomly assigned to five groups ( n = 40) from the total population of flies, with each group having five replicates. Groups of PD flies were treated with either 500 mg/kg ribose-cysteine diet, 250 mg/kg levodopa diet, or a combination of the two compounds for 21 days, whereas the control group (w 1118 ) and the PD group were exposed to a diet without ribose-cysteine or levodopa. In addition to various biochemical and neurochemical assays, longevity, larval motility, and gravitaxis assays were carried out. Locomotive capability, lifespan, fecundity, antioxidant state, and neurotransmitter systems were all significantly ( p < 0.05) compromised by overexpression of α-Syn. However, flies treated both ribose cysteine and levodopa showed an overall marked improvement in motor functions, lifespan, fecundity, antioxidant status, and neurotransmitter system functions. In conclusion, ribose-cysteine and levodopa, both singly and in combination, potentiated a therapeutic effect on alpha-synuclein transgenic Drosophila melanogaster models of Parkinsonism.

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“…Furthermore, a study also noticed the interchangeable relationship between oxidative stress and cholinergic neurons, which found that administering the ACh antagonist scopolamine increased AChE, MDA, and impaired memory learning [ 69 ]. In fact, the local release of ACh-induced glutamate release through activation of nAChR occurs in many parts of the CNS related to memory formation [ 70 ]. Infrared light proved to be able to induce excess efflux of glutamate by stimulating glutamatergic nerve endings [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

Transcranial Irradiation Mitigates Paradoxical Sleep Deprivation Effect in an Age-Dependent Manner: Role of BDNF and GLP-1

Lutfy,

Essawy,

Mohammed

et al. 2023

Neurochem Res

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The growing prevalence of aged sleep-deprived nations is turning into a pandemic state. Acute sleep deprivation (SD) accompanies aging, changing the hippocampal cellular pattern, neurogenesis pathway expression, and aggravating cognitive deterioration. The present study investigated the ability of Near Infra Red (NIR) light laser to ameliorate cognitive impairment induced by SD in young and senile rats. Wistar rats ≤ 2 months (young) and ≥ 14 months (senile) were sleep-deprived for 72 h with or without transcranial administration of NIR laser of 830 nm. Our results showed that NIR photobiomodulation (PBM) attenuated cognitive deterioration made by SD in young, but not senile rats, while both sleep-deprived young and senile rats exhibited decreased anxiety (mania)-like behavior in response to PBM. NIR PBM had an inhibitory effect on AChE, enhanced the production of ACh, attenuated ROS, and regulated cell apoptosis factors such as Bax and Bcl-2. NIR increased mRNA expression of BDNF and GLP-1 in senile rats, thus facilitating neuronal survival and differentiation. The present findings also revealed that age exerts an additive factor to the cellular assaults produced by SD where hippocampal damages made in 2-month rats were less severe than those of the aged one. In conclusion, NIR PBM seems to promote cellular longevity of senile hippocampal cells by combating ROS, elevating neurotrophic factors, thus improving cognitive performance. The present findings provide NIR as a possible candidate for hippocampal neuronal insults accompanying aging and SD.

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Acetylcholine bidirectionally regulates learning and memory

Cited by 53 publications

References 284 publications

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Discovery of Multitarget-Directed Ligands from Piperidine Alkaloid Piperine as a Cap Group for the Management of Alzheimer’s Disease

Ribose-cysteine and levodopa abrogate Parkinsonism via the regulation of neurochemical and redox activities in alpha-synuclein transgenic Drosophila melanogaster models

Transcranial Irradiation Mitigates Paradoxical Sleep Deprivation Effect in an Age-Dependent Manner: Role of BDNF and GLP-1

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