Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats

• DOI: 10.1007/s00424-024-02924-1
• Publication Date: 2024-02-28T10:02:24Z
• Authors: Dingding Lv; Bin Xiao; Huaying Liu; Linping Wang; Yingshun Li; Yin Hua Zhang; Qinghua Jin
• Keywords: 0301 basic medicine; 03 medical and health sciences; Neuroscience

Abstract Obesity has been linked with the impairment of spatial memory and synaptic plasticity but molecular mechanisms remained unidentified. Since glutamatergic transmission NMDA receptor neural pathways in hippocampal dentate gyrus (DG) are essential learning memory, we aimed to investigate glutamate (Glu) signaling DG diet-induced obesity (DIO) rats. Spatial were assessed via Morris water maze (MWM) test on control (Ctr) DIO Extracellular concentration Glu was determined using vivo microdialysis HPLC. The protein expressions subunit 2B (NR2B), brain-derived neurotrophic factor (BDNF), activation calcium/calmodulin-dependent kinase II (CaMKII) cAMP-response-element-binding (CREB) observed by western blot. impaired rats compared those Ctr. NR2B expression increased, while BDNF CaMKII CREB decreased increased Ctr 3rd 4th days MWM test, significant further increment Microinjection an antagonist (MK-801) into reversed impairment. Such effects accompanied greater CaMKII/CREB In conclusion, enhancement Glu-NMDA contributes rats, maybe modulation CaMKII-CREB-BDNF pathway.