ArticlePflugers Archiv : European journal of physiology2024
Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats.
Article in Pflugers Archiv : European journal of physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 10 citations in OpenAlex.
- Cognition at the core of metabolic syndrome: linking metabolic load to behavioural impairment in a longitudinal high-fat diet rat model.Brain, behavior, & immunity - health · 2026Article
- Linking Metabolic Disorders and Immune System Phenomena in Schizophrenia: The Role of Adipose Tissue and Inflammation.Biomedicines · 2025Review
- IDO Activation Affects BDNF/TrkB Signaling Pathway, Oxidative Stress, and Mitochondrial Enzymatic Activities in Temporal Lobe Epilepsy.Current issues in molecular biology · 2025Article
- Article
- Bangpungtongsung-san alleviates depressive-like behavior and metabolic disturbances in high-fat diet-induced obesity: mechanisms involving inflammation, CREB/BDNF signaling, and NMDA receptor modulation.Frontiers in pharmacology · 2025Article
- Dopamine and D1 receptor in hippocampal dentate gyrus involved in chronic stress-induced alteration of spatial learning and memory in rats.Neurobiology of stress · 2024Article
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7 authors at 2 institutions in 2 countries.
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Abstract
Obesity has been linked with the impairment of spatial memory and synaptic plasticity but the molecular mechanisms remained unidentified. Since glutamatergic transmission and NMDA receptor neural pathways in hippocampal dentate gyrus (DG) are essential in the learning and memory, we aimed to investigate glutamate (Glu) and NMDA receptor signaling of DG in spatial learning and memory in diet-induced obesity (DIO) rats. Spatial learning and memory were assessed via Morris water maze (MWM) test on control (Ctr) and DIO rats. Extracellular concentration of Glu in the DG was determined using in vivo microdialysis and HPLC. The protein expressions of NMDA receptor subunit 2B (NR2B), brain-derived neurotrophic factor (BDNF), the activation of calcium/calmodulin-dependent kinase II (CaMKII) and cAMP-response-element-binding protein (CREB) in the DG were observed by western blot. Spatial learning and memory were impaired in DIO rats compared to those of Ctr. NR2B expression was increased, while BDNF expression and CaMKII and CREB activation were decreased in DG of DIO rats. Extracellular concentration of Glu was increased in Ctr on the 3rd and 4th days of the MWM test, but significant further increment was observed in DIO rats. Microinjection of an NMDA antagonist (MK-801) into the DG reversed spatial learning and memory impairment. Such effects were accompanied by greater BDNF expression and CaMKII/CREB activation in the DG of DIO rats. In conclusion, the enhancement of Glu-NMDA receptor transmission in the hippocampal DG contributes to the impairment of spatial learning and memory in DIO rats, maybe via the modulation of CaMKII-CREB-BDNF signaling pathway.
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