Neuroscience
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The mitotic activity of certain tissues in the body is closely associated with circadian clock function. However, the effects of growth factors on the molecular clockwork are not fully understood. Stimulation of neural stem cells (NSCs) with epidermal growth factor (EGF), a well-known mitogen, is known to cause synchronized cell cycle progression with a period of approximately 24 h, closely associated with the Per2 gene expression rhythm. ⋯ EGF led to gene induction in the presence of cycloheximide, suggesting that de novo protein synthesis is unnecessary. Pretreatment with the MEK1/2 inhibitor U0126 significantly suppressed the acute induction of Per2, Dec1, and Noct by EGF and also abolished the EGF-induced phase shift of the PER2::LUCIFERASE rhythm in NSCs. These results suggest a unique effect of EGF on the molecular clockwork of NSCs.
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Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. ⋯ Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
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Following peripheral nerve injury, Schwann Cells (SCs) undergo dedifferentiation, proliferation, migration, and remyelination. Recent works demonstrated the importance of the short non-coding RNA (miRNAs) in SC dedifferentiation and remyelination after nerve injury. Previously, we found some miRNAs like miR-9, miR-221, miR-222 and miR-182 could regulate the proliferation and migration of SCs. ⋯ In addition, NGF1-A binding protein 1 (Nab1) which was essential for SCs myelination could be downregulated by miR-221-3p. Suppressing the expression of Nab1 could reverse the promotion of miR-221-3p antagomir on SC myelination. The effects of miR-221-3p on SC myelination might be used to improve peripheral nerve regeneration, thus offering a new approach to peripheral nerve repair.
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Survival depends on adaptation to shifting environmental risks and opportunities. Regarding risks, the mechanisms which permit acquisition, recall, and flexible use of aversive associations is poorly understood. Drawing on the evidence that the orbital frontal cortex is critical to integrating outcome expectancies with flexible appetitive behavioral responses, we hypothesized that OFC would contribute to behavioral flexibility within an aversive learning domain. ⋯ In a recall test, rats exhibit greater freezing to the CS+ than the CS-. Temporary inactivation of the ventrolateral OFC with muscimol prior to conditioning did not affect later discrimination, but inactivation after learning and prior to recall impaired discrimination between safety and danger cues. This result complements prior research in the appetitive domain and suggests that the OFC plays a general role in behavioral flexibility regardless of the valence of the CS.
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Emerging evidence suggests that acupuncture treatment has anti-oxidative effects that affect cognitive impairment in vascular dementia (VD) rats. In the present study, we aimed to investigate whether thioredoxin-1 (Trx-1)/thioredoxin reductase-1 (TrxR-1) was involved in the beneficial effects of acupuncture. After 2-weeks of acupuncture treatment, Morris water maze (MWM), dihydroethidium (DHE) staining, Nissl staining and TdT-mediated dUTP nick end labeling (TUNEL) staining were used to assess the effects of acupuncture on cognitive function and hippocampal neuronal injury in two-vessel occlusion (2VO) model. ⋯ Acupuncture also up-regulated the expressions of Trx-1 and TrxR-1, increased the activity of TrxR-1, accompanied with inhibiting the activation of the ASK1-JNK/p38 pathway. However, the effects of acupuncture on improving cognitive function, inhibiting oxidative stress and neuron apoptotic damage were blocked by Trx-1siRNA. In conclusion, these findings indicated that acupuncture treatment improved VD though anti-oxidative and anti-apoptotic mechanisms which involved the up-regulations of Trx-1/TrxR-1 and inhibitions of ASK1-JNK/p38 pathway.