Neuroscience
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Motor learning does not occur on a 'blank slate', but in the context of prior coordination solutions. The role of prior coordination solutions is likely critical in redundant tasks where there are multiple solutions to achieve the task goal - yet their influence on subsequent learning is currently not well understood. Here we addressed this issue by having human participants learn a redundant virtual shuffleboard task, where they held a bimanual manipulandum and made a discrete throwing motion to slide a virtual puck towards a target. ⋯ On the second day, all participants transferred to a common criterion task, which required an asymmetric solution. Results showed that: (i) the symmetry of the practiced solution affected motor variability during practice, with more asymmetric solutions showing higher exploration of the null space, (ii) when transferring to the common criterion task, participants in the symmetric group showed much higher null space exploration, and (iii) when no constraints were placed on the solution, participants tended to return to the symmetric solution regardless of the solution originally practiced. Overall, these results suggest that the stability of prior coordination solutions plays an important role in shaping learning in redundant motor tasks.
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Sevoflurane impairs learning and memory of the developing brain. However, strategies to mitigate these detrimental effects have been scarce. Herein, we investigated whether tetramethylpyrazine could alleviate the impairment of learning and memory and its underlying mechanisim in sevoflurane-exposed neonatal rats. ⋯ It was found that neonatal exposure of sevoflurane impaired learning and memory, increased neuronal apoptosis, altered the morphology of dendritic spine, upregulated the expressions of NMDAR2A and PSD95, and induced LTP deficits. Pretreatment with tetramethylpyrazine not only alleviated impairment of learning and memory, but also improved sevoflurane-induced changes in neuronal damage, dendritic spine morphology, NMDAR2A and PSD95 expressions, as well as LTP. These findings indicated that pretreatment with tetramethylpyrazine alleviated the impairment of learning and memory induced by sevoflurane through improvement of hippocampal synaptic plasticity in neonatal rats.
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This study investigates the therapeutic effect of astrocyte-derived extracellular vesicles (EVs) in mitigating neurotoxicity-induced transcriptome changes, mitochondrial function, and base excision repair mechanisms in human brain endothelial cells (HBECs). Neurodegenerative disorders are marked by inflammatory processes impacting the blood-brain barrier (BBB) that involve its main components- HBECs and astrocytes. Astrocytes maintain homeostasis through various mechanisms, including EV release. ⋯ High-throughput RNA sequencing revealed that exposure to Na2Cr2O7 suppressed immune response genes. The addition of astrocyte-derived EVs resulted in the dysregulation of long noncoding RNAs impacting genes associated with brain development and angiogenesis. These findings reveal the positive impact of astrocytes-derived EVs in mitigating neurotoxicity and as potential therapeutic avenues for neurodegenerative diseases.
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The adverse impact of disturbmitochondrialbiogenesis onearly brain injury (EBI) following Subarachnoid Haemorrhage (SAH) has been broadly recognized and is closely associated with oxidative stress and neuronal apoptosis. Previous studies have indicated the therapeutic potential of Ropinirole in Ischemic Stroke. However, there is a lack of evidence regarding the ability of Ropinirole to enhance mitochondrial biogenesis and quality control after Subarachnoid Haemorrhage. ⋯ Further research showed that, Ropinirole therapy inhibit Drp1-mediated fission by accelerating the activity of fusion protein Mfn2/OPA1 along with regulating the translocation of PGC1-α and SIRT3 through restricting cytochrome C inside mitochondria to maintain mitochondrial metabolism. Ropinirole exerted neuroprotective effects by improving mitochondrial activity in a PGC1-α/SIRT3-dependent way via regulating Drp1 mediated fission. The effective treatment for SAH-induced EBI may involve increasing biogenesis and inhibiting excessive mitochondrial fission with Ropinirole.
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The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. ⋯ We segmented SAS in the whole brain of 83 young adults and divided SAS into four cortical lobes. We demonstrated regional variations in FA and MD within SAS and an age-related decline in FA among young adults, indicating that diffusion within SAS becomes more isotropic with aging. These findings raise new questions about the factors influencing diffusion anisotropy within SAS, which are relevant to glymphatic transport.