Neuroscience
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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.
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Functional imaging studies have implicated the hippocampus and parahippocampal gyrus in cue-guided spatial navigation, but also many other regions. Furthermore, little is known about de-activations that take place during performance of navigation tasks, something that is of interest given that the hippocampus is a component of the default mode network, which de-activates during attention-demanding tasks. In this study 22 healthy subjects underwent whole-brain functional Magnetic Resonance Imaging (fMRI) while they navigated toward a previously learned goal in a virtual reality environment. ⋯ De-activations were seen in the medial frontal cortex and other regions of the default mode network, but not in the posterior cingulate cortex/precuneus. The findings support the involvement of the hippocampus in cue-guided navigation, but suggest that its posterior regions are particularly important. Cue-guided spatial navigation is associated with de-activation in some but not all parts of the default mode network.
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The periodontal ligament (PDL) includes several types of nerve endings, such as Aβ-, Aδ-, and C-fibers, which play critical roles in detecting the strength and direction of occlusal force. Previous studies have demonstrated that electrical stimulation of the PDL activates the somatosensory and insular cortices. However, the profile of cortical excitation in response to mechanical PDL stimulation mostly remains unknown. ⋯ A paired-pulse protocol of mechanical stimulation revealed that the amplitude of the second response was smaller than the first response, in accordance with the shorter interstimulus interval. Systemic application of morphine, a potent blocker of nociception, reduced the amplitude of the maximum excitation, particularly in S2/IOR compared to S1. These results suggest that S1 and S2/IOR are principally excited by mechanical and electrical stimulation, respectively, and that S2/IOR is involved in nociception processing.
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Few researchers have investigated the direction of commissural axon projections on the contralateral side of the vertebrate embryonic spinal cord, especially for comparison between its different regions. In this study, pCAGGS-GFP plasmid expression was limited to different regions of the chicken embryonic spinal cord (cervical, anterior limb, anterior thorax, posterior thorax and posterior limb) at E3 using in ovo electroporation with modified electrodes and optimal electroporation conditions. Then open-book technique was performed at E6 to analyze the direction of axon projections in different spinal cord regions. ⋯ The ratio of rostral and caudal projections was significantly different between the five investigated regions (P<0.05), except between the cervical region and the anterior limb (P>0.05). The projections were most likely to be rostral for the posterior limb followed by the posterior thorax, cervical region, anterior limb and anterior thorax. Our data for the direction of the commissural axon projections will be helpful in the future analyses of axon projection mechanisms and spinal cord-brain circuit formation.
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The insular cortex is a critical brain region involved in nicotine addiction. However, its specific cellular and synaptic mechanisms underlying nicotine addiction remains largely unknown. In the present study, we examined how nicotine modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex. ⋯ Blockade of GABAA receptors or β2-containing nAChRs prevented the effects of nicotine on synaptic potentiation. Taken together, these results suggest that in layer V pyramidal neurons of the insular cortex, activation of β2-containing nAChRs expressed in non-FS interneurons suppresses synaptic potentiation through enhancing GABAergic synaptic transmission. These findings provide important insights into the cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.