Effect of resveratrol on forelimb grip strength and myofibril structure in aged rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of resveratrol on muscle mass, forelimb grip strength, myofibril structure and AMPK/sirt1 pathway in skeletal muscles of aged rats.</p><p><b>METHODS</b>Twenty aged (25 months old) SD rats were randomly divided into aged control group and resveratrol treatment group (10 in each group) with 10 young (6 months old) rats served as the young control group. In resveratrol treatment group, the rats were treated with resveratrol (mixed in chow) for 6 weeks. After the treatment, the mass of the gastrocnemius was measured and the sarcopenia index (SI) was calculated as the gastrocnemius mass (mg) to body weight (g) ratio. The forelimb grip strength of the rats was measured using a electronic grip strength meter, and the lengths of the sarcomere, I-band, A-band and H-zone of the myofibrils were determined by transmission electron microscopy.</p><p><b>RESULTS</b>Compared with the young rats, the aged control rats had significantly lower SI of the gastrocnemius (P<0.05) and grip strength (P<0.05) with increased lengths of the sarcomere, A-band, I-band and H-zone (P<0.05) and lowered expressions of AMPK, P-AMPK, and sirt1 protein (P<0.05). Resveratrol treatment of the aged rats significantly increased the forelimb grip strength, reduced the lengths of sarcomere length, I-band and H-zone (P<0.05) and increased, P-AMPK, sirt1 protein expressions (P<0.05) without significantly affecting the SI (P>0.05) or the A-band length (P>0.05).</p><p><b>CONCLUSION</b>Resveratrol does not improve the muscle mass but can increase the forelimb grip strength in aged rats possibly by activating AMPK/sirt1 pathway to improve the ultrastructure of the myofibrils.</p>

Effects of ghrelin on hippocampal DKK-1 expression and cognitive function in rats with diabetes mellitus / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effects of ghrelin on learning and memory abilities and expressions of DKK-1 and β-catenin in the hippocampus of diabetic rats.</p><p><b>METHODS</b>Sixty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, ghrelin-treated diabetic group (DM1 group), and ghrelin- and D-lys3-GHRP-6 (a GHSR-1a receptor antagonist)-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (65 mg/kg). The learning and memory abilities of the rats were assessed with Morris water maze (MWM) test. The ultrastructure of the hippocampal CA1 area of the rats were observed with electron microscopy. Serum levels of DKK-1 were examined by ELISA, and the expressions of DKK-1 and β-catenin in the hippocampus were examined by quantitative real-time PCR and Western blotting.</p><p><b>RESULTS</b>Compared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05), increased expression of DKK-1 and lowered β-catenin expression in the hippocampus (P<0.05), significant ultrastructural injuries and disordered arrangement of neurons with the nuclear pycnosis in the hippocampal CA1 area. Ghrelin treatment of the diabetic rats obviously improved their learning and memory abilities (P<0.05), reduced DKK-1 and increased β-catenin expressions (P<0.05), ameliorated ultrastructural damages in the hippocampal CA1 area and restored normal neuronal alignment with clear cell layers. Such effects of ghrelin were antagonized by treatment with D-lys3-GHRP-6 in the diabetic rats.</p><p><b>CONCLUSION</b>Ghrelin can alleviate learning and memory dysfunction in diabetic rats possibly by down-regulating the expressions of DKK-1 and activating the WNT signaling pathways.</p>

Intracerebroventricular administrations of angiotensin IV (Ang IV) ameliorate cognitive disorder in diabetic rats

Cognitive impairment is a common complication of diabetes. Hippocampus plays an important role in cognitive function. In hyperglycemia, synaptophysin, a crucial synaptic vesicle membrane protein in hippocampus neuron is found to be down-regulated. Recent evidences have shown that angiotensin IV can facilitate memory acquisition and recovery. However, whether it can also improve cognitive functions of diabetic rats with cognitive disorder, and the possible mechanisms are uncertain. Hence, the objectives of this study. Forty fi ve Sprague Dawley male rats were randomly divided into three groups: Control, diabetic group and diabetes with angiotensin IV treatment group. The cognitive functions, mainly learning and memory of the rats were evaluated using Morris water maze task. The synapses ultrastructure, relative mRNA concentrations and protein expression levels of synaptophysin in hippocampus CA1 area were estimated using transmission electron microscope, RT-PCR, immunohistochemistry and western blotting, respectively. Our study showed that in the diabetic rats with angiotensin IV treatment, the cognitive impairment as measured by Morris water maze task improved, the ultrastructure of synapses in hippocampus reversed, the relative mRNA concentrations and protein levels of synaptophysin in hippocampus signifi cantly increased, when compared with diabetic rats. We conclude that angiotensin IV plays an important role in improving cognitive function of diabetic rats. The possible mechanisms are up-regulating the expression of synaptophysin and normalizing the ultrastructure of synapses in hippocampus.