Effects of treadmill exercise on brain insulin signaling and β-amyloid in intracerebroventricular streptozotocin induced-memory impairment in rats

Abstract

Purpose: The purpose of the study is to explore effect of 6 weeks treadmill exercise on brain insulin signaling and β-amyloid(Aβ).

Methods: The rat model of Alzheimer's disease(AD) used in the present study was induced by the intracerebroventricular(ICV) streptozotocin(STZ). To produce the model of animal with AD, STZ(1.5mg/kg) was injected to a cerebral ventricle of both cerebrums of Sprague-Dawley rat(20 weeks). The experimental animals were divided into ICV-Sham(n=7), ICV-STZ CON(n=7), ICV-STZ EXE(n=7). Treadmill exercise was done for 30 min a day, 5 days a week for 6 weeks. Passive avoidance task was carried out before and after treadmill exercise.

Results: The results of this study show that treadmill exercise activated Protein kinase B(AKT)/ Glycogen synthase kinase 3α (GSK3α), possibly via activation of insulin receptor(IR) and insulin receptor substrate(IRS) and reduced Aβ in the brain of ICV-STZ rats. More interestingly, treadmill exercise improved cognitive function of ICV-STZ rats. Finally, physical exercise or physical activity gave positive influences on brain insulin signaling pathway.

Conclusion: Therefore, treadmill exercise can be applied to improve AD as preventive and therapeutic method.

Keywords: brain insulin signaling; intracerebroventricular-streptozotocin injection; treadmill exercise; β-amyloid.

Fig. 1.

EFFECT OF TREADMILL EXERCISE ON THE LATENCY TIME OF THE PASSIVE AVOIDANCE TASK. VALUES ARE MEAN ± SEM 7 ANIMALS/GROUPS

Fig. 2.

EXPRESSION AND IMMUNOSTAINING ANALYSIS OF Β-AMYLOID LEVEL IN THE HIPPOCAMPUS OF ICV-SHAM, ICV-STZ CON AND ICV-STZ EXE. WESTERN BLOT (N = 4) AND IMMUNO STAINING ANALYSIS (N = 3) OF Β-AMYLOID DEPOSITION. A,B) PVDF FILTERS TRANSFERRING 30ΜG OF PROTEIN FROM THE CORTEX AND HIPPOCAMPUS OF EACH GROUP, INCUBATED WITH ANTI-HUMAN Β -AMYLOID ANTIBODY. THE BANDS WERE QUANTIFIED BY DENSITOMETRY TO OBTAIN RELATIVE LEVELS OF Β-AMYLOID. GAPDH WAS PROBED AS AN INTERNAL CONTROL. C) IMMUNOSTAINING OF AΒ-42. 40ΜM-THICK SECTIONS OF BRAINS FROM EACH GROUP WERE INCUBATED WITH ANTI-HUMAN Β-AMYLOID PRIMARY ANTIBODY AND HRP-CONJUGATED GOAT ANTI-RABBIT IGG. A SCALE BAR REPRESENTS 100㎛. VALUES ARE PRESENTED AS MEANS ± SEM.

Fig. 3.

Effect of treadmill exercise on activation of brain insulin signaling in the hippocampus of ICV-Sham, ICV-STZ CON and ICV-STZ EXE. A) The levels of brain insulin signaling in the hippocampus was analyzed by western blots. GAPDH was probed as an internal control. B) Acticvation of brain insulin signaling was normalized with respect to ICV-Sham. Values are mean ± SEM 4 animals/groups.