Repeated treatment with alpha 7 nicotinic acetylcholine receptor ligands enhances cognitive processes and stimulates Erk1/2 and Arc genes in rats

Potasiewicz, Agnieszka; Faron-Górecka, Agata; Popik, Piotr; Nikiforuk, Agnieszka

doi:10.1016/j.bbr.2021.113338

Cited by 7 publications

(6 citation statements)

References 67 publications

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“…7,32 It has been speculated if KA's antagonistic effect on the α7 nAChR contribute, as α7 nAChR agonists have shown positive effects on cognitive function and memory in rats. 33 Along with KA, concentrations of Pic, also assumed to be neuroprotective, were higher among the patients with AD. Pic is known to mildly inhibit QA's neurotoxic effects by chelating zinc.…”

Section: Discussionmentioning

confidence: 96%

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Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease

Knapskog

Aksnes

Edwin

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONThe kynurenine pathway's (KP) malfunction is closely related to Alzheimer's disease (AD), for antagonistic kynurenic acid (KA) and agonistic quinolinic acid act on the N‐methyl‐D‐aspartate receptor, a possible therapeutic target in treating AD.METHODSIn our longitudinal case–control study, KP metabolites in the cerebrospinal fluid were analyzed in 311 patients with AD and 105 cognitively unimpaired controls.RESULTSPatients with AD exhibited higher concentrations of KA (β = 0.18, P < 0.01) and picolinic acid (β = 0.20, P < 0.01) than the controls. KA was positively associated with tau pathology (β = 0.29, P < 0.01), and a higher concentration of KA was associated with the slower progression of dementia.DISCUSSIONThe higher concentrations of neuroprotective metabolites KA and picolinic acid suggest that the activation of the KP's neuroprotective branch is an adaptive response in AD and may be a promising target for intervention and treatment.Highlights Patients with Alzheimer's disease (AD) exhibited higher concentrations of kynurenic acid and picolinic acid than controls. Higher concentrations of kynurenic acid were associated with slower progression of AD. Potential neurotoxic kynurenines were not increased among patients with AD. Activation of the kynurenine pathway's neuroprotective branch may be an adaptive response in AD.

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Section: Discussionmentioning

confidence: 96%

“…However, KA's effects may be bidirectional, given animal models showing that high levels of KA can weaken cognition 7,32 . It has been speculated if KA's antagonistic effect on the α7 nAChR contribute, as α7 nAChR agonists have shown positive effects on cognitive function and memory in rats 33 …”

Section: Discussionmentioning

confidence: 99%

Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease

Knapskog

Aksnes

Edwin

et al. 2023

Alzheimer's & Dementia

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“…Most pharmacological experiments assessing the role of nAChRs in memory processing have been performed by using agonist, antagonist or allosteric modulators via systemic administration (Palandri et al, 2021; Potasiewicz et al, 2021; Wang et al, 2020). However, α7 nAChRs are also expressed in peripheral cells, including lymphocytes, macrophages and endothelial cells (Ayala Peña et al, 2011; Sato et al, 1999; Zanetti et al, 2016).…”

Section: The Role Of α7 Nachrs In Brain Regions Involved In Memory Pr...mentioning

confidence: 99%

“…Another neurological disorder where cognitive impairment is a core clinical symptom is schizophrenia (Green et al, 2019). Preclinical studies have shown that α7 nAChR agonists, partial agonists and positive allosteric modulators have pro‐cognitive effects in a variety of animal models (Potasiewicz et al, 2021; Terry & Callahan, 2020; Unal et al, 2021). Despite extensive preclinical and clinical research assessing the role of nAChRs as key elements on the pathophysiology of cognitive deficits in schizophrenia, it seems that there is no strong evidence to consider α7 nAChR agonists as add‐on treatment to antipsychotics to improve cognition in schizophrenia (reviewed by Koola, 2021; Recio‐Barbero et al, 2021; Letsinger et al, 2022).…”

Section: α7 Nachr As a Pharmacotherapy Tool In Memory Deficits And Co...mentioning

confidence: 99%

α7 nicotinic acetylcholine receptor in memory processing

Pastor

Medina

2023

Eur J of Neuroscience

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Information storage in the brain involves different memory types and stages that are processed by several brain regions. Cholinergic pathways through acetylcholine receptors actively participate on memory modulation, and their disfunction is associated with cognitive decline in several neurological disorders. During the last decade, the role of α7 subtype of nicotinic acetylcholine receptors in different memory stages has been studied. However, the information about their role in memory processing is still scarce. In this review, we attempt to identify brain areas where α7 nicotinic receptors have an essential role in different memory types and stages. In addition, we discuss recent work implicating—or not—α7 nicotinic receptors as promising pharmacological targets for memory impairment associated with neurological disorders.

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“…Impaired Arc protein synthesis is associated with various brain pathologies, including memory disorders, Alzheimer's disease, autism spectrum disorders, schizophrenia, and epilepsy (60)(61)(62). Arc cellular pathways have emerged as key regulators of synaptic plasticity, and are becoming known for being central players in genetic risk for many neural disorders (20).…”

Section: Possible Involvement Of Arc In the Mechanisms Of Neuropsychi...mentioning

confidence: 99%

Arc protein, a remnant of ancient retrovirus, forms virus-like particles, which are abundantly generated by neurons during epileptic seizures, and affects epileptic susceptibility in rodent models

Sibarov,

Tsytsarev,

Volnova

et al. 2023

Front. Neurol.

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A product of the immediate early gene Arc (Activity-regulated cytoskeleton-associated protein or Arc protein) of retroviral ancestry resides in the genome of all tetrapods for millions of years and is expressed endogenously in neurons. It is a well-known protein, very important for synaptic plasticity and memory consolidation. Activity-dependent Arc expression concentrated in glutamatergic synapses affects the long-time synaptic strength of those excitatory synapses. Because it modulates excitatory-inhibitory balance in a neuronal network, the Arc gene itself was found to be related to the pathogenesis of epilepsy. General Arc knockout rodent models develop a susceptibility to epileptic seizures. Because of activity dependence, synaptic Arc protein synthesis also is affected by seizures. Interestingly, it was found that Arc protein in synapses of active neurons self-assemble in capsids of retrovirus-like particles, which can transfer genetic information between neurons, at least across neuronal synaptic boutons. Released Arc particles can be accumulated in astrocytes after seizures. It is still not known how capsid assembling and transmission timescale is affected by seizures. This scientific field is relatively novel and is experiencing swift transformation as it grapples with difficult concepts in light of evolving experimental findings. We summarize the emergent literature on the subject and also discuss the specific rodent models for studying Arc effects in epilepsy. We summarized both to clarify the possible role of Arc-related pseudo-viral particles in epileptic disorders, which may be helpful to researchers interested in this growing area of investigation.

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Repeated treatment with alpha 7 nicotinic acetylcholine receptor ligands enhances cognitive processes and stimulates Erk1/2 and Arc genes in rats

Cited by 7 publications

References 67 publications

Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease

Higher concentrations of kynurenic acid in CSF are associated with the slower clinical progression of Alzheimer's disease

α7 nicotinic acetylcholine receptor in memory processing

Arc protein, a remnant of ancient retrovirus, forms virus-like particles, which are abundantly generated by neurons during epileptic seizures, and affects epileptic susceptibility in rodent models

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