Neuroscience
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Acute itch is elicited by histamine, as well as non-histaminergic itch mediators including chloroquine, BAM8-22 and Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL). When injected intradermally, histamine binds to histamine H1 and H4 receptors that activate transient receptor potential vanilloid 1 (TRPV1) to depolarize pruriceptors. Chloroquine, BAM8-22, and SLIGRL, respectively, bind to Mas-related G-protein-coupled receptors MrgprA3, MrgprC11, and MrgprC11/PAR2 that in turn activate transient receptor potential ankyrin 1 (TRPA1). ⋯ Pretreatment with the TRPV1 antagonist AMG-517 (10 or 20 μg), but not the TRPA1 antagonist HC-030031 (50 or 100 μg), significantly attenuated the magnitude and time course of thermal hyperalgesia and mechanical allodynia elicited by histamine (p < 0.001 for both), indicating that these effects are mediated by TRPV1. In contrast, pretreatment with the TRPA1 antagonist significantly reduced thermal hyperalgesia and mechanical allodynia elicited by chloroquine (p < 0.001 for both ), BAM-822 (p < 0.01, p < 0.001, respectively) and SLGRL (p < 0.05, p < 0.001, respectively), indicating that effects elicited by these non-histaminergic itch mediators require TRPA1. TRPV1 and TRPA1 channel inhibitors thus may have potential use in reducing hyperalgesia and allodynia associated with histaminergic and non-histaminergic itch, respectively.
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This is the first study to examine the influence of activity in one limb on corticospinal excitability to the contralateral limb during a locomotor output. Corticospinal and spinal excitability to the biceps brachii of the ipsilateral arm were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of corticospinal axons, respectively. Responses were evoked during the mid-elbow extension position of arm cycling across three different cycling tasks: (1) bilateral arm cycling (BL), (2) unilateral, contralateral cycling with the ipsilateral arm moving passively (IP), and (3) unilateral, contralateral cycling with the ipsilateral arm at rest (IR). ⋯ TMES-evoked cervicomedullary MEP (CMEPs) amplitudes followed a similar pattern of task-dependent modulation, with BL having the smallest CMEPs and IR having the largest. In line with our previous findings, MEP amplitudes increased and CMEP amplitudes decreased as the cadence increased from 60 to 90 rpm. We suggest that the higher corticospinal excitability to the ipsilateral limb during the IP and IR conditions was predominantly due to disinhibition at both the cortical and spinal levels.
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The nervous system relies upon correct interconnections to exert its normal function. During vertebrate embryonic development, highly stereotyped scaffolds of axon tracts are formed early in the brain to set the foundation for the neuronal interconnections. During zebrafish early development, anterior dorsal telencephalic (ADt) neurons extend axons along the ipsilateral supraoptic tract (SOT) and the contralateral anterior commissure (AC). ⋯ Here we show ectopic activation of Wnt signaling abolishes the ipsilateral SOT originating from the ADt neurons. Further mechanistic studies show ectopic activation of Wnt signaling significantly reduces Slits' expression, whilst mis-expression of Slit3 rescues SOT outgrowth. Together, our findings indicate Wnt signaling controls the ipsilateral axonal outgrowth through the regulation of slits' expression in the zebrafish forebrain.
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Recently, circular RNAs (circRNAs) have been revealed to be an important non-coding element of the transcriptome. The brain contains the most abundant and widespread expression of circRNA. There are also indications that the circular transcriptome undergoes dynamic changes as a result of brain ageing. ⋯ These changes in expression were validated by RT-qPCR. We provide the first comprehensive survey of the circular transcriptome in mammalian synapses, thereby paving the way for future studies. Additionally, we present 16 genes that express solely circRNAs, without linear RNAs co-expression, exclusively in young and aged synaptosomes, suggesting a synaptic gene network that functions along canonical splicing activity.
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Changes in perineuronal nets (PNNs) after hearing loss were described in previous studies. The present study aimed to examine how single-sided deafness (SSD) affects the expression of excitatory and inhibitory synaptic transporters and PNNs in the primary auditory cortex (A1). Sprague-Dawley rats (8-week-old females, n = 30) were divided into three groups: (1) the SSD 2-week group (n = 10), (2) the SSD 4-week group (n = 10), and (3) the 4-week control group (n = 10). ⋯ The SSD groups had elevated expression levels of metalloproteinase (MMP) 9 on the contralateral side. The presynaptic glutamatergic and GABAergic transporters were increased in the A1 on the ipsilateral side after induction of SSD. Changes in the cortical auditory nervous system accompanied changes in the PNNs and their degradation enzymes MMP9 and MMP14.