Neuroscience
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It has been shown that brain-injured patients (BIP) have exacerbated mirror movements (MM). MM are involuntary contractions occurring in homologous muscles contralateral to voluntary movements, particularly in distal upper limb muscles. Attentional and inhibitory processes have been proposed as key factors to explain the level of MM. ⋯ Moreover, (3) in all participants - independent of the type of task used to evaluate MM - the amount and intensity of MM was predicted by the level of executive control, assessed by the Trail Making Test. High level of MM was associated with weak executive control abilities. This study is the first to highlight the link between MM and executive functioning, which may have implications for rehabilitation in BIP.
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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 indicates that transcriptome alterations due to epigenetic deregulation concur to ALS pathogenesis. Accordingly, pan-histone deacetylase (HDAC) inhibitors delay ALS development in mice, but these compounds failed when tested in ALS patients. Possibly, lack of selectivity toward specific classes of HDACs weakens the therapeutic effects of pan-HDAC inhibitors. ⋯ Conversely, increase in specific Class II HDACs (-4, -5 and -6) occurs in skeletal muscle of mice with severe neuromuscular impairment. Importantly, treatment with MC1568 causes early improvement of motor performances that vanishes at later stages of disease. Notably, motor improvement is not paralleled by reduced motor neuron degeneration but by increased skeletal muscle electrical potentials, reduced activation of mir206/FGFBP1-dependent muscle reinnervation signaling, and increased muscle expression of myogenic genes.
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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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Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD. However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. ⋯ Our biochemical data showed that EE-induced neuroprotection occurs in combination with multiple synergic neuroprotective pathways: (1) increased neurogenesis shown by an increase in BrdU-positive neurons; (2) diminished loss of dopaminergic neurons evidenced by upregulated tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels; (3) increased antioxidant capacity (e.g., CuZnSOD, CATALASE, GPX1/2, HO-1, DJ1 and PRXIII); and (4) enhanced autophagy (LC3 II, p62, BECLIN1, BNIP3, LAMP2, CATHEPSIN L and TFEB). Our study suggests that EE-induced multiple synergic protective pathways including enhanced neurogenesis, antioxidative capacity, and concordant autophagy promotion contribute to restoration of impaired dopaminergic neuronal function caused by PD. Thus, PD patients should be encouraged to actively participate in regular EE as a potent nonpharmacological therapeutic strategy against PD.