Modulation of glycine sites enhances social memory in rats using PQQ combined with d-serine

Zhou, Xingqin; Liu, Dong; Zhang, Rongjun; Peng, Ying; Qin, Xiaofeng; Mao, Shishi

doi:10.1016/j.bbr.2016.04.034

Cited by 4 publications

(4 citation statements)

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“…Pharmacological studies in rats and mice also revealed deficits in social memory after administration of NMDA receptor antagonists, such as MK-801 [101,140,141,142,143], PCP [63,144,145] and ketamine [146] (Table 2). Conversely, enhancement of the NMDA receptor function by targeting either the glutamate-binding site with NMDA [147] or the glycine-binding site was shown to enhance social recognition memory in rodents.…”

Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

“…Conversely, enhancement of the NMDA receptor function by targeting either the glutamate-binding site with NMDA [147] or the glycine-binding site was shown to enhance social recognition memory in rodents. As such, D-serine, a full agonist of the glycine-binding site of the NMDA receptors, was shown to prolong social memory in rats [140] and to improve the MK-801-induced deficits in social memory [143]. Pyrroloquinoline quinone (PQQ), a powerful neuroprotectant that specifically binds to the glycine-binding site of the brain NMDA receptors, also improved the MK-801-induced deficits in social memory and even accentuated the effects of D-serine when administered in combination [143].…”

Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

“…As such, D-serine, a full agonist of the glycine-binding site of the NMDA receptors, was shown to prolong social memory in rats [140] and to improve the MK-801-induced deficits in social memory [143]. Pyrroloquinoline quinone (PQQ), a powerful neuroprotectant that specifically binds to the glycine-binding site of the brain NMDA receptors, also improved the MK-801-induced deficits in social memory and even accentuated the effects of D-serine when administered in combination [143]. Inhibition of glycine transporter 1 with the GlyT1-inhibitors N[3-(4′-flurophenyl)-3-(4′-phenylphenoxy) propyl]sarcosine (NFPS) and 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidin-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (TASP0315003), which increase the NMDA receptor function by indirectly activating the glycine-binding site, was shown to enhance social recognition in treatment-naïve rats and to prevent the MK-801-induced deficits in social memory [101,140].…”

Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

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The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents

Zoicas

Kornhuber

2019

IJMS

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The appropriate display of social behaviors is essential for the well-being, reproductive success and survival of an individual. Deficits in social behavior are associated with impaired N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. In this review, we describe recent studies using genetically modified mice and pharmacological approaches which link the impaired functioning of the NMDA receptors, especially of the receptor subunits GluN1, GluN2A and GluN2B, to abnormal social behavior. This abnormal social behavior is expressed as impaired social interaction and communication, deficits in social memory, deficits in sexual and maternal behavior, as well as abnormal or heightened aggression. We also describe the positive effects of pharmacological stimulation of the NMDA receptors on these social deficits. Indeed, pharmacological stimulation of the glycine-binding site either by direct stimulation or by elevating the synaptic glycine levels represents a promising strategy for the normalization of genetically-induced, pharmacologically-induced or innate deficits in social behavior. We emphasize on the importance of future studies investigating the role of subunit-selective NMDA receptor ligands on different types of social behavior to provide a better understanding of the underlying mechanisms, which might support the development of selective tools for the optimized treatment of disorders associated with social deficits.

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Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

Section: Role Of the Nmda Receptors In Social Memorymentioning

confidence: 99%

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The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents

Zoicas

Kornhuber

2019

IJMS

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“…More exactly, glutamate and dopamine confusion are involved in the development of schizophrenia and the abnormal expression of NMDA receptors is thought to contribute to negative symptoms and cognitive deficits [8]. Up to now, cognitive impairment remains an unresolved main problem in schizophrenic patients [9]. Changes in NMDA-R expression may have a different modality depending on the applied neuroleptics.…”

Section: Introductionmentioning

confidence: 99%

Modulating NMDA receptors to treat MK-801-induced schizophrenic cognition deficit: effects of clozapine combining with PQQ treatment and possible mechanisms of action

et al. 2020

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Background: Clozapine has remarkable efficacy on both negative and cognitive symptoms of schizophrenia due to its slight activation of NMDA receptor. In fact, much evidence to the contrary. NMDAR is a complex containing specific binding sites, which are regulated to improve negative symptoms and cognitive deficits associated with individuals affected by schizophrenia. PQQ is a powerful neuroprotectant that specifically binds with NMDA receptors in the brain to produce beneficial physiological and cognitive outcomes. The aim of this study was to enhance NMDAR function and improve cognitive ability in schizophrenia by PQQ combined with clozapine. Methods: Rats were divided into four groups (n = 5) including control (saline), model (MK-801, 0.5 mg•kg − 1 •d − 1), atypical antipsychotic (MK-801 (0.5 mg•kg − 1 •d − 1) + Clozapine (1.0 mg•kg − 1 •d − 1), and co-agonist NMDA receptor (MK-801 (0.5 mg•kg − 1 •d − 1) + Clozapine (0.5 mg•kg − 1 •d − 1) + PQQ (1.0 μg•kg − 1 •d − 1) group. Each group of rats was injected subcutaneously every day for 6 weeks. Behavior test, including stereotyped behavior, locomotor hyperactivity, learning and memory, was performed. The Western blot assay was performed to analyze the expression of GSK-3β, Akt, NMDAR1, and MGLUR in rat hippocampus. Results: Results indicated that clozapine and PQQ combination therapy can improve MK801-induced schizophrenia behavior including stereotyped behavior, locomotor hyperactivity and cognitive impairment. Furthermore, we found that modulating NMDA receptors could ameliorate the memory impairments in Mk-801 induced schizophrenia rats by reducing the expression of NMDAR1 and MGLUR3, decreasing hippocampal tau hyperphosphorylation and inhibiting apoptosis through Akt /GSK-3β signaling pathway.

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S-Adenosylmethionine Metabolism and Aging

Loenen

2018

Epigenetics of Aging and Longevity

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Modulation of glycine sites enhances social memory in rats using PQQ combined with d-serine

Cited by 4 publications

References 41 publications

The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents

The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents

Modulating NMDA receptors to treat MK-801-induced schizophrenic cognition deficit: effects of clozapine combining with PQQ treatment and possible mechanisms of action

S-Adenosylmethionine Metabolism and Aging

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