Neuroscience
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Activation of the M1 muscarinic acetylcholine receptor (M1R) may be an effective therapeutic approach for Alzheimer's disease (AD), dementia with Lewy bodies, and schizophrenia. Previously, the M1R/M4R agonist xanomeline was shown to improve cognitive function and exert antipsychotic effects in patients with AD and schizophrenia. However, its clinical development was discontinued because of its cholinomimetic side effects. ⋯ Other than in the orbital cortex and claustrum, TAK-071 induced similar c-Fos expression patterns. When donepezil was co-administered to increase the levels of acetylcholine, the number of TAK-071-induced c-Fos-positive cells in these brain regions was increased. TAK-071, through induction of similar neural activation as that seen with xanomeline, may produce procognitive and antipsychotic effects with improved cholinergic side effects.
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White matter lesions due to cerebral hypoperfusion may be an important pathophysiology in vascular dementia and stroke, although the inherent mechanisms remain to be fully elucidated. The present study, using a mouse model of chronic cerebral hypoperfusion, examined the white matter protective effects of levetiracetam, an anticonvulsant, via the signaling cascade from the activation of cAMP-responsive element binding protein (CREB) phosphorylation. Mice underwent bilateral common carotid artery stenosis (BCAS), and were separated into the levetiracetam group (injected once only after BCAS [LEV1] or injected on three consecutive days [LEV3]), the vehicle group, or the anti-epileptic drugs with different action mechanisms phenytoin group (PHT3; injected on three consecutive days with the same condition as in LEV3). ⋯ The activation of microglia and astrocytes was markedly suppressed, although the number of oligodendrocyte precursor cells (OPCs) and GST-pi-positive-oligodendrocytes was markedly higher in the cerebral white matter. Moreover, oxidative stress was significantly reduced. We found that 3-day treatment with levetiracetam maintained SV2A protein expression via interaction with astrocytes, which influenced the OPC lineage through activation of CREB to protect white matter from ischemia.
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The topographic map of motor cortical representation, called the motor map, is not invariant, but can be altered by motor learning, neurological injury, and functional recovery from injury. Although much attention has been paid to short-term changes of the motor map, robust measures have not been established. The existing mapping methods are time-consuming, and the obtained maps are confounded by time preference. ⋯ Although the motor threshold of the hotspot was not changed, the area in which it was decreased appeared caudally to the hotspot, which may be in the somatosensory cortex. The present study demonstrated rapid enlargement of the forelimb motor map in the order of a few minutes induced by skin stimulation. This helps to understand the spatial dynamism of motor cortical representation that is modulated rapidly by somatosensory input.
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Inflammation may result in periventricular leukomalacia, which is the leading cause of preterm brain encephalopathy. Moreover,
-3 polyunsaturated fatty acids ( -3 PUFAs) play a pivotal role against central nervous system injury, which is likely related to its anti-inflammatory effect. However, the mechanism regarding the remedial effects of -3 PUFA for LPS-induced neuro-injury has remained unclear. ⋯ Interestingly, this phenomenon became more noticeable with the combined application of -3 PUFA and a PI3K/AKT agonist. In conclusion, we confirm that -3 PUFA plays an important role in neuroprotection by activating the PI3K/AKT/β-catenin pathway. It may be a promising strategy against brain injury. -
The aim of this study was to investigate the effect of paradoxical sleep deprivation (PSD) on the BDNF-related miRNA expression in ovariectomized (OVX) rats. The animals were randomly divided into eight groups (control, PSD, wide platform, sham surgery, anti-miR-191, anti-miR-191/PSD, scrambled and PSD in intact). Bilateral-ovariectomy was performed one month before the experiment in the OVX rats. ⋯ Intracerebroventricular (ICV) injection of anti-miR-191a improved the down-regulation of BDNF and attenuated PSD-induced cognitive impairment. Hippocampal BDNF is probably one of the targets of miR-191a in sleep-deprived OVX rats. Our results suggest that miR-191a may be increased in the sleep-deprived OVX rats to regulate BDNF levels.