Modulation of glycine sites enhances social memory in rats using PQQ combined with d-serine.
The aim of study was to investigate the effects of pyrroloquinoline quinone (PQQ) combined with d-serine on the modulation of glycine sites in the brain of rats using social recognition test. Rats were divided into seven groups (n=10) and given repeated intraperitoneal (ip) injections of saline, MK-801 (0.5mg/kg), clozapine (1mg/kg), haloperidol (0.1mg/kg), d-serine (0.8g/kg), PQQ (2.0μg/kg), or d-serine (0.4g/kg) combined with PQQ (1.0μg/kg) for seven days. A social recognition test, including assessment of time-dependent memory impairment, was performed. A non-competitive NMDA receptor antagonist, MK-801, significantly impaired social memory, and this impairment was significantly repaired with an atypical antipsychotic (clozapine) but not with a typical antipsychotic (haloperidol). Likewise, d-serine combined with PQQ significantly improved MK-801-disrupted cognition in naïve rats, whereas haloperidol was ineffective. The present results show that the co-agonist NMDA receptor treated with PQQ and d-serine enhances social memory and may be an effective approach for treating the cognitive dysfunction observed in schizophrenic patients. PQQ stimulates glycine modulatory sites by which it may antagonize indirectly by removing glycine from the synaptic cleft or by binding the unsaturated site with d-serine in the brain, providing the insights into future research of central nervous system and drug discovery.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. Electronic address: zhouxingqin@jsinm.org.
Xingqin
X
Zhou
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Dong
D
Liu
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Rongjun
R
Zhang
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Ying
Y
Peng
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Xiaofeng
X
Qin
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Shishi
S
Mao
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000633:toxicity; D004340:Drug Contamination; D004357:Drug Synergism; D005998:Glycine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology; D045542:PQQ Cofactor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000494:pharmacology*; D012919:Social Behavior; D013997:Time Factors
D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D012694:Serine; D016291:Dizocilpine Maleate; D045542:PQQ Cofactor; D003024:Clozapine; D006220:Haloperidol; D005998:Glycine
Co-agonist NMDA receptor; Glycine sites; PQQ; Schizophrenic; d-serine