Neuroscience
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12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia-induced memory impairment and cholinergic deficits. ⋯ The inhibition of 12/15 LOX resulted in a significant decrease in NO levels in the hippocampal homogenate associated with downregulated iNOS, nNOS transcription but not eNOS speculating that 12/15 LOX is critically involved in HIF-1α, mediated by nitric oxide-induced neurotoxicity. We also observed a similar effect of 12/15 LOX inhibition on hippocampal COX2 expression. 12/15LOX inhibition could effectively modulate central cholinergic indices during hypobaric hypoxia by restoring mAChR-1, α7NAChR expression and AChE, ChAT activity in the hippocampus comparable to normal mice. We report here the mechanistic involvement of 12/15LOX in orchestrating hypoxia-associated neuronal damage and HIF-1α-dependent neuroinflammation resulting in cognitive decline.
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The application of subsensory noise stimulation over the lower limbs has been shown to improve proprioception and postural control under certain conditions. Whereas the effect specificity seems to depend on several factors, studies are still needed to determine the appropriate method for training and rehabilitation purposes. In the current study, we investigated whether the application of subsensory electrical noise over the legs improves proprioceptive function in young and older adults. ⋯ On the other hand, the magnitude of postural sway was reduced by noise stimulation only during a more challenging task, namely, when the optical flow was changing in an unpredictable (nonperiodic) manner. No differential effects of stimulation between groups were observed. These findings suggest that the relevance of proprioceptive inputs in tasks with different challenges, but not the subjects' age, is a determining factor for sensorimotor improvements due to electrical noise stimulation.
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Randomized Controlled Trial
Role of capsaicin- and heat-sensitive afferents in stimulation of acupoint induced pain and analgesia in humans.
We investigated role of capsaicin-sensitive afferents within and without the areas of Zusanli (ST36)/Shangjuxu (ST37) acupoints along the stomach (ST) meridian in the perception and modulation of pain assessed by visual analog scale of pain and its distribution rated by subjects, pressure pain threshold (PPT), and heat pain threshold (HPT) in humans. Compared with the treatment of non-acupoint area, capsaicin (100µg/50µl) administered into either ST36 or ST37 acupoint caused the strongest pain intensity and the most extensive pain distribution, followed by rapid onset, bilateral, long-lasting secondary mechanical hyperalgesia and slower onset secondary heat hypoalgesia (1day after the capsaicin treatment). ⋯ Upon trapezius muscle pain elicited by the i.m. injection of 5.8% saline, pre-emptive treatment of the contralateral ST36 acupoint with 43°C heating-needle stimulation alleviated the ongoing muscle pain, reduced painful area, and reversed the decrease in HPT. It is suggested that (1) pain elicited from the acupoint and non-acupoint areas differs significantly, which are supposed to be dependent on the different distributions and contributions of capsaicin-sensitive afferents. (2) Non-painful heat stimulation is a valid approach in prevention of ongoing muscle pain with associated post-effects of peripheral and central sensitization.
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Epilepsy is one of the most common chronic neurological conditions worldwide. The current poor understanding and lack of reliable biomarkers of the epileptogenic process are the major limitations in the development of anti-epileptic drugs that are able to prevent or modify the underlying disease. ⋯ Here we review the advances of different in vivo imaging techniques, including magnetic resonance-based and nuclear imaging-based modalities, in animal models of epilepsy. Together these techniques can be applied to visualize and quantify structural, metabolic, functional and molecular changes in longitudinal study designs to provide unique information about early pathophysiological changes and their interplay involved in epileptogenesis, monitoring the disease progression, assessing the effectiveness of possible therapies, and potentially identify translatable biomarkers for clinical use.
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Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs) in dopaminergic neurons. α-Synuclein (α-syn), a major protein component of LBs, is known to regulate synaptic plasticity, with a crucial role in memory and motor function in the central nervous system. Levodopa (L-3,4-dihydroxyphenylalanine; also known as L-DOPA) is considered the most effective medication for controlling the symptoms of PD. However, it is unclear whether L-DOPA improves the neuropathology of PD. ⋯ Our data showed that L-DOPA could attenuate ER stress markers, including the levels of activating transcription factor 4 (ATF4), C/EBPhomologous protein expression (CHOP), immunoglobulin-heavy-chain-binding protein (BiP), sliced X-box-binding protein 1 (XBP-1), and reduce nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling through dopamine receptor D2 (DRD2) in SH-SY5Y neuronal cells under α-syn-induced toxicity. In conclusion, we suggest that L-DOPA may attenuate the neuropathology of PD by regulating signaling related to DRD2 in neuronal cells under α-syn-induced toxicity. Our study, therefore, indicates an additional role for L-DOPA in the treatment of PD.