title: Changes in hippocampal synaptic functions and protein expression in monosodium glutamate-treated obese mice during development of glucose intolerance.
abstract: Glucose is the sole neural fuel for the brain and is essential for cognitive function. Abnormalities in glucose tolerance may be associated with impairments in cognitive function. Experimental obese model mice can be generated by an intraperitoneal injection of monosodium glutamate (MSG; 2 mg/g) once a day for 5 days from 1 day after birth. MSG-treated mice have been shown to develop glucose intolerance and exhibit chronic neuroendocrine dysfunction associated with marked cognitive malfunctions at 28-29  weeks old. Although hippocampal synaptic plasticity is impaired in MSG-treated mice, changes in synaptic transmission remain unknown. Here, we investigated whether glucose intolerance influenced cognitive function, synaptic properties and protein expression in the hippocampus. We demonstrated that MSG-treated mice developed glucose intolerance due to an impairment in the effectiveness of insulin actions, and showed cognitive impairments in the Y-maze test. Moreover, long-term potentiation (LTP) at Schaffer collateral-CA1 pyramidal synapses in hippocampal slices was impaired, and the relationship between the slope of extracellular field excitatory postsynaptic potential and stimulus intensity of synaptic transmission was weaker in MSG-treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the CA1 region of MSG-treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in MSG-treated mice during the development of glucose intolerance, though it remains unknown whether impaired LTP is due to altered inhibitory transmission. It may be important to examine changes in glucose tolerance in order to prevent cognitive malfunctions associated with diabetes.
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Sachie
authors: S
authors: Sasaki-Hamada
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Yuki
authors: Y
authors: Hojo
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Hajime
authors: H
authors: Koyama
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Hayuma
authors: H
authors: Otsuka
authors: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
authors: Jun-Ichiro
authors: J
authors: Oka
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology* / Q000523:psychology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D009473:Neuronal Plasticity; D009765:Obesity / Q000150:complications*; D018091:Receptors, AMPA / Q000378:metabolism; D012970:Sodium Glutamate; D009435:Synaptic Transmission; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000199:Actins; D018091:Receptors, AMPA; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D012970:Sodium Glutamate
keywords: VGluT; diabetes; glutamate receptor; hippocampal synaptic plasticity; obesity