BackgroundCyclo (his-pro-CHP) plus zinc (Zn + 2 ) (Cyclo-Z) is the only chemical agent known to stimulate IDE synthesis and reduction of inactive cellular insulin fragments.
ObjectivesThe aim of this study was to characterize the effects of Cyclo-Z on insulin pathway, memory functions and brain oscillations in the Alzheimer's disease (AD) rat model.
MethodsThe rat model of AD was established by bilateral injection of Aβ42 oligomer (2,5nmol/10µl) into the lateral ventricles. Cyclo-Z (10mg Zn + 2 /kg and 0,2mg CHP/kg, daily) was administered orally by gavage for 21 days. At the end of the experimental period, memory tests and electrophysiological recordings were performed which followed by the biochemical analysis.
ResultsAβ42 oligomers led to a signi cant increase in fasting blood glucose, serum insülin, Homeostatic Model Assessment for Insulin Resistance(HOMA-IR) and phospho-tau-Ser356 levels. Moreover, Aβ42 oligomers caused a signi cant decrement in body weight, hippocampal insulin, brain insulin receptor substrate(IRS-Ser612), and glycogen synthase kinase-3 beta(GSK-3β) levels. Also, Aβ42 oligomers resulted in a signi cant reduction in memory. The Cyclo-Z treatment prevented the observed alterations in the ADZ group except for phospho-tau levels and attenuated the increased Aβ42 oligomers levels in the ADZ group. We also found that the Aβ42 oligomer decreased the left temporal spindle and delta power during ketamine anesthesia. Cyclo-Z treatment reversed the Aβ42 oligomer-related alterations in the left temporal spindle power.
ConclusionsCyclo-Z prevents Aβ oligomer-induced changes in the insulin pathway, amyloid toxicity, and may contribute to the improvement of memory de cits and neural network dynamics in this rat model.
OBJECTIVES: This study aims to investigate the acute effects of thymoquinone (TQ) which has been suggested to be a cardioprotective agent, on ventricular myocytes. METHODS: Freshly isolated rat ventricular myocytes were exposed to TQ and using standard whole-cell patch-clamp technique action potential (AP), sodium current (I Na ), L-type calcium current (I CaL ) and transient outward potassium current (I to ) were measured. RESULTS: TQ prolonged the duration of AP and decreased the peak value compared to that of control myocytes. Consistently, it inhibited I Na in a concentration-dependent manner and shifted the channel kinetics to more hyperpolarized voltages. Besides, TQ not only inhibited I to and I CaL but also signifi cantly attenuated the isoproterenol-induced increase in I CaL . CONCLUSION: The effect of TQ on cardiomyocytes has been demonstrated for the fi rst time. TQ changes AP morphology along with ionic currents and alleviates β-adrenergic response in adult ventricular myocytes. These results indicate that TQ may be considered as a therapeutic agent in cases such as diabetic cardiomyopathy and cardiac hypertrophy, wherein the β-adrenergic system is over-activated (Tab. 2, Fig. 6, Ref. 30).
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