Recurrent/moderate hypoglycemia induces hippocampal dendritic injury, microglial activation, and cognitive impairment in diabetic rats

• Main Authors: Won Seok, Yoo Byung, Kauppinen Tiina M, Choi Bo, Kim Jin, Jang Bong, Lee Min, Sohn Min, Liu Jialing, Swanson Raymond A, Suh Sang
• Format: Article
• Language: English
• Published: BMC 2012-07-01
• Series: Journal of Neuroinflammation
• Subjects: Recurrent/moderate hypoglycemia; Dendrite; Superoxide; Lipid peroxidation; Neuron death; Microglial activation; NADPH oxidase; Apocynin
• Online Access: http://www.jneuroinflammation.com/content/9/1/182

<p>Abstract</p> <p>Background</p> <p>Recurrent/moderate (R/M) hypoglycemia is common in type 1 diabetes. Although mild or moderate hypoglycemia is not life-threatening, if recurrent, it may cause cognitive impairment. In the present study, we sought to determine whether R/M hypoglycemia leads to neuronal death, dendritic injury, or cognitive impairment.</p> <p>Methods</p> <p>The experiments were conducted in normal and in diabetic rats. Rats were subjected to moderate hypoglycemia by insulin without anesthesia. Oxidative stress was evaluated by 4-Hydroxy-2-nonenal immunostaining and neuronal death was determined by Fluoro-Jade B staining 7 days after R/M hypoglycemia. To test whether oxidative injury caused by NADPH oxidase activation, an NADPH oxidase inhibitor, apocynin, was used. Cognitive function was assessed by Barnes maze and open field tests at 6 weeks after R/M hypoglycemia.</p> <p>Results</p> <p>The present study found that oxidative injury was detected in the dendritic area of the hippocampus after R/M hypoglycemia. Sparse neuronal death was found in the cortex, but no neuronal death was detected in the hippocampus. Significant cognitive impairment and thinning of the CA1 dendritic region was detected 6 weeks after hypoglycemia. Oxidative injury, cognitive impairment, and hippocampal thinning after R/M hypoglycemia were more severe in diabetic rats than in non-diabetic rats. Oxidative damage in the hippocampal CA1 dendritic area and microglial activation were reduced by the NADPH oxidase inhibitor, apocynin.</p> <p>Conclusion</p> <p>The present study suggests that oxidative injury of the hippocampal CA1 dendritic region by R/M hypoglycemia is associated with chronic cognitive impairment in diabetic patients. The present study further suggests that NADPH oxidase inhibition may prevent R/M hypoglycemia-induced hippocampal dendritic injury.</p>