Mechanisms Of Diabetes Impairing Learning Performance And The Protective Effect Of ω-3PUFAs

Diabetes mellitus is a heterogeneous metabolic disorder characterized byhyperglycemia resulting from defective insulin secretion, resistance to insulin action orboth. Poor academic performance in diabetic children and memory impairment in adultswith diabetes are viewed as increasing public health concerns. In humans, diabetesmellitus is associated with moderate impairments in cognitive function and patientspresent a high risk of affective disorders, dementia and Alzheimer disease. Learning andmemory deficits also occur in streptozotocin (STZ)-induced diabetic rats. At present, themechanism of diabetes-induced learning and memory deficits is largely unclear, and theeffective medical method is still on research. Therefore, it is necessary to further study thebiological mechanism and seek protective measures to allevate the damage to the bodyand reduce the huge consumption of social resources.The present study was designed to establish diabetic animal model, and investigatethe effect of diabetes on special learning and memory by behavioral test, and explore itsmechanisms. Furthermore, the preventive effect of omega-3polyunsaturated fatty acids(ω-3PUFAs) on diabetes-induced learning and memory deficits were investigated.Methods:1. The animal model of diabetes was established by STZ injection with SD male rats.2. Spatial learning task were performed with Morris water maze4weeks after STZinjection. Nissl stain, transmission electron microscope (TEM), immunohistochemical method, and Western-Blot technique were used to detect the morphological andultramicro-structureal changes, cell apoptosis and the expression of related proteins inhippocampus.3. The neuron excitability and ionic currents were detected with in vitro patch-clamprecording on brain slices.4. Animals were gave ω-3PUFAs rich diet for a week before STZ injection.Immunohistochemical method, TEM and Western-Blot were used to detect themophalogical and ultramicro-structureal changes, cell apoptosis and the expression ofrelated proteins in hippocampus. patch-clamp recording was used to detect theneuron excitability and ionic currents.Results:1. The results of the Morris water maze showed that the latency and the exploringdistance had similar tendencies in both diabetic and control group during the training.The rats were likely behaving nearer the area of platform. But diabetic group spendsignificantly more time than control group in excape latency.（P <0.05）.2. The Nissl stain showed less neuron in CA1area of hippocampus in diabetic rats.Loosed range of cells and large quantity of bubles were observed. TEM showsobvious damage of ultramicro-structure. Immunohistochemical mesurements showedthe apoptosis of CA1neurons increased in diabetic rats and the Bax and Caspase-3positive neurons were also increased.3. By western-Blot detection, we found that the expression of apoptosis related proteinsBax and Caspase-3increased in hippocampus. Both Bax and Cyt-c trans-lacationwere observed. Bax tranfered from cytoplasm to mitichondria and Cyt-c released frommitichondria into cytoplasm.4. The sodium currents decreased and the potassium currents increased, which maycontribute to the decreased excitability of CA1pyramidal neurons.5. After ω-3PUFAs treatment, the escape latency significantly decreased comparing tothe diabetic rats in Morris water maze. The morphological damage and apoptosis ofCA1pyramidal neurons in hippocampus was relieved and the excitability of neuronsincreased comparing to diabetic rats. Conclusions:1. Behavioral test suggested that diabetes induces learning and memory deficits in rats.2. Diabetes induced morphological change and apoptosis of hippacampal neurons, whichwas related to the mitochondrial function. The change of neurons affected the function,which may be the cytology foundation of effects of diabetes on learning and memory.3. Diabetes decreased the excitability of hippocampal neurons, which may be thefunctional foundation of effects of diabetes on learning and memory.4. ω-3PUFAs attenuated the damages of diabetes on hippocampal neurons, and protectedthe ability of learning and memory of diabetic rats by improving the neuronalfunction.