Abstract
Persistent hyperglycaemia and scopolamine were used to inflict amnesia in rats. Chronic hyperglycaemia causes metabolic impairment, neuronal dysfunction and oxidative stress causing cognitive impairment. This study aimed to determine anti amnesic activities of vitamin D, epalrestat and their combination against diabetes and scopolamine induced cognitive dysfunction. A total of eighty-eight Wistar albino rats, eleven groups, and 8 rats/Gr., were used. Type 2 diabetes mellitus was induced in all groups, except Gr.1 which was treated with 2 ml normal saline. Gr. 2 to 11 by feeding high fat diet for 28 days followed by single dose streptozotocin 35 mg/kg i.p. Hyperglycemic rats were screened with blood sugar level > 200 mg/dL. Gr. 2 rats were treated with only streptozotocin and Gr. 3 to 6 were treated with streptozotocin and test drugs donepezil 1 mg/kg, vitamin D, 27 mcg/kg, epalrestat 57 mg/kg, vitamin D + epalrestat, per oral, respectively. Gr. 7 rats were treated with only streptozotocin + scopolamine and all others from Gr. 8 to 11 were treated with streptozotocin + scopolamine and donepezil, vitamin D, epalrestat, vitamin D + epalrestat respectively. The gold standard behavioural tests were conducted by using Morris water maze and passive avoidance paradigms after 30–60 min of inj. scopolamine, 0.5 mg/kg, intra-peritoneal. Hippocampal tissue was taken for histopathological and biochemical evaluation. Rats treated with donepezil, vitamin D, epalrestat and vitamin D + epalrestat showed significant improvement in behavioural, biochemical and histopathological parameters as compared to streptozotocin and (streptozotocin + scopolamine) treated rats. This study underscores cognition enhancing abilities of vitamin D and epalrestat, and their combination in diabetic rats with and without scopolamine.
Highlights
Diabetes Mellitus (DM) is a dynamic metabolic disease that can have debilitating effects on numerous organ systems in the body, including the nervous system, through a variety of mechanisms (Kodl and Seaquist 2008)
Probe trial: Percentage of time spent and distance travelled in target zone In reference to Figs. 1 and 2, in probe trial conducted on day 5, the percentage of time spent and percentage of distance travelled in target zone by rats treated with STZ and (STZ ? scopolamine) decreased significantly (p \ 0.001) as compared to control rats
It was observed that the percentage of time spent and percentage of distance travelled in target zone by groups treated with donepezil, vitamin D, epalrestat and increased significantly (p \ 0.05) as compared to the STZ group
Summary
Diabetes Mellitus (DM) is a dynamic metabolic disease that can have debilitating effects on numerous organ systems in the body, including the nervous system, through a variety of mechanisms (Kodl and Seaquist 2008). One of the well-recognized but less addressed complications of Cognitive Neurodynamics exacerbated development of reactive oxygen species and weakened antioxidant defences (Li et al 2016). The hippocampus and the amygdala are important in the consolidation of learning and memory. Hippocampus is mainly involved in consolidation of declarative memory (Halbach 2007). Short-term memory conversion into long-term memory is severely affected when hippocampus is damaged. Spatial memory is affected in case of hippocampal damage (Burgess et al 2001)
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