The TrkB agonist 7,8-dihydroxyflavone improves sensory-motor performance and reduces lipid peroxidation in old mice

Abstract

7,8-Dihydroxyflavone (7,8-DHF) is a natural flavonoid compound that act as Trk-B agonist. 7,8-DHF is also a potent antioxidant. When applied systematically, 7,8-DHF can pass through bloodbrain barrier and exhibit potential therapeutic effects in several animal models of neurodegenerative disorders. This study investigates the remedial effects of 7,8-DHF on behavioral impairments and biochemical changes associated with aging with a species emphasis on cortex. For this purpose three experimental groups were formed which are young control group, old group and old-DHF groups. 5 mg/kg 7,8-DHF was administered intraperitoneally to old-DHF group for 3 weeks. We assessed the hang wire and adhesive removal performances of mice. Also, oxidative stress, neuroinflammation and synaptic protein levels in the cortex were measured. We observed that chronic administration of 7,8-DHF improved behavioral performance of old mice. Besides, 7,8-DHF reversed MDA level which was increased in old control animals. However, 3 weeks application of 7,8-DHF failed to recover the levels of neuroinflammation markers (TNF-α and IL-6) and synaptic proteins (PSD-95 and Synaptophysin) which were reduced in old group. These findings demonstrate that improvement of age-dependent behavioral impairments and MDA levels by 7,8-DHF could be attributed to its antioxidant actions.

Yaşa bağlı oksidatif stres ve nitrik oksid azalışında 7,8-dihidroksiflavonun etkisi

“…Based on present results, we concluded that administration of 7,8-DHF alleviates hepatic and renal oxidative stress in some degree, as well as nitric oxide depletion in liver, kidney and heart tissues. While previous studies have shown that 7,8-DHF presents anti-aging properties on dermal fibroblast cells [34], reduces memory loss by inhibiting agerelated changes in hippocampal cells [7], and reduces lipid peroxidation in cerebral cortex and improves sensory motor performance in aged mice [8] for the first time in this study, we demonstrated that 7,8-DHF exihibited favorable effects on age related oxidative stress and/or NO depletion in non-neural tissues. However, as a major shortcoming of our study, the presence of oxidative stress and how it was affected by 7,8-DHF treatment should be supported by other classical parameters such as protein oxidation and antioxidant enzyme activities.…”

“…Using TrkB receptor agonist 7,8-dihydroxyflavone (DHF), Zeng et al [7] observed that age-related memory impairment and synaptic plasticity relieved in aged rats. In our previous study, we showed that 7,8-DHF improved sensory motor performance and reduced lipid peroxidation of brain cortex in aged mice [8].…”

“…7,8-DHF (Sigma-Aldrich 38183-03-8) was administered to the DHF-elderly group daily (5 mg/kg, intraperitoneally, ip) for 3 weeks. Intraperitoneally vehicle (17% DMSO, ip) was administered to young and elderly groups for 3 weeks [8]. In our study, the number of subjects was determined as 10 for each group.…”

Effects of housing conditions on stress, depressive like behavior and sensory-motor performances of C57BL/6 mice

“…Hang wire test was used to evaluate the grip strength, balance and endurance of mice [ 16 , 17 ]. As detailed in our previous study [ 18 ], the mouse was placed on a stretched wire with a thickness of 0.2 cm. The mouse had to support its body weight with its forelimbs.…”

“…The time of the first touch to the adhesive and time of removal of the adhesive reflect sensorimotor performance [ 19 , 20 ]. As previously described [ 18 ], a 3 × 3 mm square, red adhesive tape strips were stuck to the front paws of the mice. The time to touch one of the tapes with their nose or mouth and the time to remove each tape were used for statistical comparisons.…”