Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats

Abstract

Type 2 diabetes and chronic heavy alcohol consumption each have been known to be associated with the impairment of hippocampus-dependent cognitive functions. Although both conditions often coexist clinically and there is accumulated evidence of a relationship between the two, the combined effect on hippocampal long-term potentiation (LTP) has not yet been investigated. We compared the effect of type 2 diabetes itself with that of type 2 diabetes with chronic heavy alcohol consumption on the hippocampal LTP using Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, which resembles the characteristics of human type 2 diabetes. Ten of 16-week-old male OLETF rats were randomized into two treatment groups according to weight: the OLETF–Alcohol (O–A, n = 5) and the OLETF–Control (O–C, n = 5). The rats in the O–A group were fed Lieber-DeCarli Regular EtOH over a 10-week period and the amount of alcohol consumption was 8.42 ± 2.52 g/kg/day. To ensure the effect of poor glycemic control on LTP, intraperitoneal glucose tolerance test was performed after a 10-week treatment. The hippocampal LTP was measured by extracellular field excitatory post-synaptic potentials at Shaffer collateral (SC) synapses in the CA1 region. Although the O–A group showed significantly lower fasting and postprandial glucose ( P < 0.01 and P = 0.02, respectively), the hippocampal LTP was more significantly attenuated in the O–A group than the O–C group ( P = 0.032). The results of this study suggested that chronic heavy alcohol consumption could potentiate the impairment of hippocampal LTP in individuals with impaired glucose tolerance or early type 2 diabetes, even though it did not aggravate, but did improve glycemic control. Clinical attention to chronic heavy drinking will be required in preventing cognitive impairment in individuals with type 2 diabetes.