Abstract
BackgroundTo investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus.MethodsA rat model of type 2 diabetes mellitus (T2DM) was established using high fat diet and streptozotocin (30 mg/kg, ip). Insulin sensitivity was evaluated by the oral glucose tolerance test and the insulin tolerance test. After 7 weeks, the T2DM rats were treated with JZD. The step-down test and Morris water maze were used to evaluate behavior in T2DM rats after 5 weeks of treatment with JZD. Levels of phosphorylated proteins involved in the ERS and in insulin signaling transduction pathways were assessed by Western blot for T2DM rats’ hippocampus.ResultsCompared to healthy control rats, T2DM rats initially showed insulin resistance and had declines in acquisition and retrieval processes in the step-down test and in spatial memory in the Morris water maze after 12 weeks. Performance on both the step-down test and Morris water maze tasks improved after JZD treatment. In T2DM rats, the ERS was activated, and then inhibited the insulin signal transduction pathways through the Jun NH2-terminal kinases (JNK) mediated. JZD treatment suppressed the ERS, increased insulin signal transduction, and improved insulin resistance in the rats’ hippocampus.ConclusionsTreatment with JZD improved cognitive function in the T2DM rat model. The possible mechanism for DACD was related with ERS inducing the insulin signal transduction dysfunction in T2DM rats’ hippocampus. The JZD could reduce ERS and improve insulin signal transduction and insulin resistance in T2DM rats’ hippocampus and as a result improved the cognitive function.
Highlights
To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus
The activity of Jun NH2-terminal kinase (JNK) protein is significantly elevated in various tissues in type 2 diabetes mellitus (T2DM) patients and animal models, which can impair insulin signaling transduction and lead to insulin resistance through activating the serine phosphorylation of insulin receptor substrate-1 (IRS-1) [4]
Assessment of T2DM rat model Healthy male Sprague–Dawley (SD) rats were fed with a high-fat diet
Summary
To investigate the effects of treatment with Multi component Chinese Medicine Jinzhida (JZD) on behavioral deficits in diabetes-associated cognitive decline (DACD) rats and verify our hypothesis that JZD treatment improves cognitive function by suppressing the endoplasmic reticulum stress (ERS) and improving insulin signaling transduction in the rats’ hippocampus. There has been growing apprehension about the complications of diabetes, especially diabetes-associated cognitive decline (DACD). The exact mechanisms of DACD have not been fully elucidated, it is known that impaired insulin signaling transduction involved in the metabolism of Amyloid Protein (Aβ) and tau [3] plays an important role in DACD. JNK is an important downstream signal of the endoplasmic reticulum stress (ERS) response. We hypothesized that ERS-induced JNK activation impairs insulin signaling transduction, resulting in DACD in the hippocampus of T2DM rats
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