Neuroscience
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Exercise induces neuroplasticity in descending motor pathways facilitating motor learning, and as such it could be utilized as an intervention in neurorehabilitation, for example when re-learning motor skills after stroke. To date, however, the neurophysiological and molecular mechanisms underlying exercise-induced neuroplasticity remain largely unknown impeding the potential utilization of exercise protocols as 'motor learning boosters' in clinical and non-clinical settings. Here, we assessed corticospinal excitability, intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS) and serum biochemical markers including brain-derived neurotrophic factor (BDNF), total and precursor cathepsin B (tCTSB, proCTSB), uncarboxylated and carboxylated osteocalcin (unOCN, cOCN) and irisin using ELISA. ⋯ We also determined that greater increases in BDNF were associated with increases in unOCN and irisin and decreases in cOCN only in participants who underwent HIIE, suggesting that unOCN and irisin may contribute to exercise-induced BDNF increases. Conversely, no changes other than a decrease in serum unOCN/tOCN were found in No Exercise participants. The present findings show that a single session of HIIE is sufficient to modulate corticospinal excitability and to increase BDNF and unOCN in sedentary, healthy males.
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We investigated whether intermittent theta burst stimulation (iTBS) can improve the spatial cognitive function of rats with hypertension-induced cerebral small vessel disease. To prove our hypothesis, stroke-prone renovascular hypertensive rats (RHRSPs) were treated with iTBS beginning at postoperative week 22. The Morris water maze was performed to assess spatial cognitive function. ⋯ The distribution of GluR1, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBa-1) in the CA1 and CA3 regions and dentate gyrus (DG) of the hippocampus were evaluated by immunofluorescence analysis. Treatment with iTBS significantly improved the spatial cognitive function of RHRSPs, increased the expression of NR2B, p-CaMKIIα and GluR1 in the hippocampus, and decreased the proliferation of astrocytes and microglia. Our results showed that iTBS treatment had a beneficial effect on the cognitive impairments induced by cerebral small vessel disease, potentially through the activation of the NR2B-CaMKII pathway, an increase in GluR1 expression and the suppression of astrocyte and microglial activation.
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Proximodistal heterogeneity in learning-promoted pathway-specific plasticity at dorsal CA1 synapses.
Contextual learning requires the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus. However, proximodistal heterogeneity of pathway-specific plasticity remains unclear. Here, we examined the proximodistal heterogeneity in learning-induced plasticity at the CA1 synapses with inputs from the entorhinal cortex layer III (ECIII) or from CA3. ⋯ Moreover, trained rats exhibited higher paired-pulse ratios at ECIII-CA1 synapses of intermediate and distal, but not proximal CA1 neurons, which suggested region-specific presynaptic plasticity. Finally, learning was clearly prevented by the bilateral microinjection of a plasticity blocker in the proximal or intermediate, but not distal CA1 subfields, which suggested functional heterogeneity along the proximodistal axis. Understanding region- and pathway-specific plasticity at dorsal CA1 synapses could aid in controlling encoded memory.
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The day-active tree shrew may serve as an animal model of human-like diurnal rhythms. However, the molecular basis for circadian rhythms in this species has remained unclear. In the present study, we investigated the expression patterns of core circadian genes involved in transcriptional/translational feedback loops (TTFLs) in both central and peripheral tissues of the tree shrew. ⋯ Additionally, the peripheral clock was phase-advanced relative to the brain clock, as there was a significant advance (2-4 h) for PER3, DBP, NR1D1 and NR1D2. Furthermore, these genes exhibited an anti-phasic relationship between the diurnal tree shrew and the nocturnal mouse (i.e., 12-h phasing differential). Collectively, our findings demonstrate a characteristic expression pattern of core circadian genes in the tree shrew, which may provide a means for elucidating molecular mechanisms of diurnal rhythms.
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Inflammatory damage following ICH is often attributed to microglia/macrophage activation. In many diseases, IL-4 has been proven to switch microglia/macrophages from the pro-inflammatory to the anti-inflammatory subtype. However, the role and underlying mechanism of IL-4 in ICH, especially in neuroprotection, remain unknown. ⋯ We verified that IL-4 mediates inflammation by regulating M1/M2 polarization in ICH and explored the underlying mechanism. Furthermore, we discovered that pathway components and apoptosis-related proteins showed consistent trends based on their respective roles, and inferred that the process that TNF-α activates caspase-3 may be the crosstalk that microglia phagocytosis developed into accelerate apoptosis of cells in ICH. In conclusion, our study demonstrates that IL-4 may promote M2 microglia/macrophage polarization partly through the JAK1/STAT6 pathway to alleviate neuroinflammation after ICH.