ABSTRACT
Neonatal hypoxia can induce the persisting brain dysfunctions and subsequently result in the behavioral abnormalities in adulthood. Improving mitochondrial functions were suggested as the effective strategy for brain functional recovery. In this study, we tested the effects of physical exercise, a well-established way benefits mitochondrion, for its functions to prevent hypoxia induced adult behavioral dysfunctions and the underlying molecular mechanism. Mice was induced with hypoxia and treadmill running were then administrated until the adulthood. The treadmill running resulted in the improved behavioral performance in depressive and anxiety tests together with the enhancement of hippocampal neurogenesis. We then detected treadmill running restored the mitochondrial morphology in adult neural stem cells (NSCs) as well as the ATP production in hippocampal tissue. In addition, activity of AMPK, which playing key roles in regulating mitochondrial functions, was also elevated by treadmill running. Blockage of AMPK with selective inhibitor compound C prohibited effects of treadmill running in attenuating neonatal hypoxia induced neurogenic impairment and antidepressant behavioral deficits in adulthood. In conclusion, treadmill running could prevent neonatal hypoxia induced adult antidepressant dysfunctions and neurogenic dampening via AMPK-mediated mitochondrial regulation.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Depression/therapy , Hypoxia/psychology , Mitochondria/metabolism , Neural Stem Cells/cytology , Animals , Animals, Newborn , Behavior, Animal , Cell Differentiation , Depression/metabolism , Depression/pathology , Disease Models, Animal , Exercise Test , Female , Hippocampus/cytology , Hypothalamo-Hypophyseal System/physiology , Hypoxia/therapy , Mice, Inbred C57BL , Neural Stem Cells/metabolism , Physical Conditioning, Animal , Pituitary-Adrenal System/physiologyABSTRACT
Physical exercise is well-established paradigm for improving adult neurogenesis and brain functions. As considered as an alternative therapeutic strategy, treadmill running could reduce cognitive impairment and psychiatric abnormalities associating post-traumatic stress disorder (PTSD), which might associate with the promote effects to adult neurogenesis. In current study, we aimed to address how treadmill exercise benefit adult hippocampal neurogenesis in PTSD model and the underlying molecular mechanism related with Akt signaling. PTSD was induced by exposure to aggressor and treatments were conducted with different intensity of compulsory treadmill running. We observed treadmill running improved hippocampal neurogenesis including proliferation and neural differentiation of neural stem cells (NSCs). Moreover, behavioral tests showed treadmill could attenuate the cognitive deficit and depressive/anxiety like behaviors in correlating with PTSD model. Moreover, treadmill running recovered the Akt activity in hippocampus. Interrupting treadmill running administrated mice with Akt inhibitor GSK690693 resulted in the blocked the effects of treadmill running to hippocampal neurogenesis and behavioral improvement in PTSD mice model. In conclusion, treadmill running could mediate behavioral functions and improve hippocampal neurogenesis in PTSD model by regulating Akt signaling.
Subject(s)
Anxiety/therapy , Behavior, Animal/physiology , Cognitive Dysfunction/therapy , Depression/therapy , Exercise Therapy , Hippocampus/physiology , Neurogenesis/physiology , Proto-Oncogene Proteins c-akt/metabolism , Running/physiology , Signal Transduction/physiology , Stress Disorders, Post-Traumatic/therapy , Animals , Anxiety/etiology , Behavior, Animal/drug effects , Cognitive Dysfunction/etiology , Depression/etiology , Disease Models, Animal , Hippocampus/drug effects , Male , Memory, Short-Term/physiology , Mice , Mice, Inbred C57BL , Neurogenesis/drug effects , Oxadiazoles/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Stress Disorders, Post-Traumatic/complications , Stress Disorders, Post-Traumatic/physiopathologyABSTRACT
This work reports a one-step simple synthesis method for functionalized reduced graphene oxide (RGO) nanosheets by a Platanus orientalis leaf extract polyphenol-mediated deoxygenation of graphene oxide (GO). Microscopic and spectroscopic characterization revealed the successful deoxygenation of GO and subsequent stabilization by oxidized polyphenols of plant extract. X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction analyses were used to examine the reduction of GO. Fourier-transform infrared spectroscopy results revealed capping of RGO with oxidized polyphenols of Platanus orientalis extract, which prevented aggregation of graphene sheets. Transmission electron microscopy and atomic force microscopy images revealed the formation of thin, transparent, sheet-like graphene. The in vitro cytotoxicity of synthesized RGO exhibited a dose-dependent toxicity against cardiac cell lines of Catla catla. Further, this work opens up a green synthesis route for the development of new graphene-based technologies.
