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

Journal of Neuroinflammation

Sang Won Suh⁴  Raymond A Swanson³  Jialing Liu¹  Min Sohn²  Min Woo Lee⁴  Bong Geom Jang⁴  Jin Hee Kim⁴  Bo Young Choi⁴  Tiina M Kauppinen³  Byung Hoon Yoo⁵  Seok Joon Won³ 

[1] Department of Neurosurgery, University of California San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA;Inha University, Department of Nursing, Incheon, Korea;Department of Neurology, University of California at San Francisco and Veterans Affairs Medical Center, San Francisco, CA, USA;Department of Physiology, Hallym University, College of Medicine, Chuncheon, 200-702, Korea;Department of Anesthesiology, Inje Paik Hospital, Inje University, School of Medicine, Seoul, Korea

关键词: Apocynin;    NADPH oxidase;    Microglial activation;    Neuron death;    Lipid peroxidation;    Superoxide;    Dendrite;    Recurrent/moderate hypoglycemia;   

Others  :  1160342
DOI  :  10.1186/1742-2094-9-182

 received in 2012-04-30, accepted in 2012-07-06,  发布年份 2012

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusion

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.

【 授权许可】

   
2012 Won et al.; licensee BioMed Central Ltd.

【 图 表 】

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