Changes in hippocampal synaptic functions and protein expression in monosodium glutamate‐treated obese mice during development of glucose intolerance

<jats:title>Abstract</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">MSG</jats:styled-content>; 2 mg/g) once a day for 5 days from 1 day after birth. <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐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 <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐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 <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐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 (<jats:styled-content style="fixed-case">LTP</jats:styled-content>) at Schaffer collateral–<jats:styled-content style="fixed-case">CA</jats:styled-content>1 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 <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐treated mice. The protein levels of vesicular glutamate transporter 1 and GluA1 glutamate receptor subunits decreased in the <jats:styled-content style="fixed-case">CA</jats:styled-content>1 region of <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐treated mice. These results suggest that deficits in glutamatergic presynapses as well as postsynapses lead to impaired synaptic plasticity in <jats:styled-content style="fixed-case">MSG</jats:styled-content>‐treated mice during the development of glucose intolerance, though it remains unknown whether impaired <jats:styled-content style="fixed-case">LTP</jats:styled-content> 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.</jats:p>