Monosodium glutamate exposure during the neonatal period leads to cognitive deficits in adult Sprague-Dawley rats

•MSG exposure during neonatal period increased tau phosphorylation.•MSG exposure during neonatal period decreased dendritic spine density and synaptic proteins.•Adult SD rats treated with MSG during neonatal period showed cognitive deficits. Epidemiological surveys show that 70–80% of patients with Alzheimer’s disease (AD) have type 2 diabetes mellitus (T2DM) or show an abnormality of blood glucose levels. Therefore, an increasing number of evidence has suggested that diabetic hyperglycemia is tightly linked with the pathogenesis and progression of AD. In the present study, we replicated T2DM animal model via subcutaneous injection of newborn Sprague-Dawley (SD) rats with monosodium glutamate (MSG) during the neonatal period to investigate the effects and underlying mechanisms of hyperglycemia on cognitive ability. We found that neonatal MSG exposure induced hyperglycemia as well as Alzheimer-like learning and memory deficits with decreased dendritic spine density and hippocampal synaptic-related protein expression and increased phosphorylated tau levels in ∼3-month-old SD rats. Our results suggested that hyperglycemia probably causes cognitive impairment and Alzheimer-like neuropathological changes, which provide the experimental data connecting T2DM and AD.