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Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats

Abstract

Rationale

Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Diabetes and dementia have become a major public health concern worldwide. At this point of time, it is very important to find the possible pharmacological agents which may be useful in management and therapy of dementia including Alzheimer’s disease, vascular dementia, etc.

Objectives

To investigate the effect of sodium butyrate on streptozotocin (STZ) diabetes induced vascular dementia in rats.

Methods

Diabetes and subsequent endothelial dysfunction and dementia were induced in rats by administration of single dose of STZ. Drug treatment was started after 1 month of STZ administration and treatment was continued until the end of the study. Morris water maze (MWM) test was employed for testing learning and memory. Endothelial function was measured on isolated aortic rings using student physiograph. Serum glucose, body weight, serum nitrite/nitrate, aortic superoxide anion generation, brain thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH) levels, and acetylcholinesterase activity were also tested.

Results

STZ treatment produced endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate, and increase in serum glucose, aortic and brain oxidative stress (increased superoxide anion, TBARS, and decreased GSH levels), and brain acetylcholinesterase activity. Treatment of sodium butyrate attenuated diabetes induced impairment of learning, memory, endothelial function, and various biochemical parameters.

Conclusions

Sodium butyrate may be considered as potential pharmacological agent for the management of diabetes induced vascular dementia.

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Acknowledgments

Authors are thankful to the Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, Punjab, India for providing all the necessary facilities and funding to conduct this research. We are also thankful to Mr. A.S. Jaggi, Assistant Prof. Pharmacology for his valuable suggestions.

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Correspondence to Nirmal Singh.

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Sharma, B., Singh, N. Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats. Psychopharmacology 215, 677–687 (2011). https://doi.org/10.1007/s00213-011-2164-0

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Keywords

  • Alzheimer
  • Dementia
  • Diabetes
  • HDAC
  • Endothelial dysfunction
  • Streptozotocin
  • Morris water maze
  • Nitrite/nitrate
  • Oxidative stress
  • Acetylcholinesterase activity