Neuroscience
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Human obesity is associated with increased leptin levels and pain, but the specific brain regions and neurochemical mechanisms underlying this association remain poorly understood. This study used adult male C57BL/6J (B6, n=14) mice and leptin-deficient, obese B6. Cg-Lep(ob)/J (obese, n=10) mice to evaluate the hypothesis that nociception is altered by systemic leptin levels and by adenosine A₁ receptors in the pontine reticular formation. ⋯ Microinjection of SMLA into the pontine reticular formation before SPA did not alter PWL. The results show for the first time that pontine reticular formation administration of the adenosine A₁ receptor agonist SPA produced antinociception only in the presence of systemic leptin. The concentration-response data support the interpretation that adenosine A₁ receptors localized to the pontine reticular formation significantly alter nociception.
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Enteric viscerofugal neurons are mechanosensory interneurons that form the afferent limb of intestino-intestinal reflexes involving prevertebral sympathetic neurons. Fast synaptic inputs to viscerofugal neurons arise from other enteric neurons, but their sources are unknown. We aimed to describe the origins of synaptic inputs to viscerofugal neurons by mapping the locations of their cell bodies within the myenteric plexus. ⋯ The cellular sources of synaptic inputs to viscerofugal neurons were located both orally and aborally (19 oral, 19 aboral), but the amplitude of oral inputs was consistently greater than aboral inputs (13.1 ± 4.3 mV vs. 10.1 ± 4.8 mV, respectively, p<0.05, paired t-test, n=6). Most impaled viscerofugal neurons were nitric oxide synthase (NOS) immunoreactive (20/27 cells tested). Thus, the synaptic connections onto viscerofugal neurons within the myenteric plexus suggest that multiple enteric neural pathways feed into intestino-intestinal reflexes, involving sympathetic prevertebral ganglia.
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Decreased levels of soluble ubiquitin carboxy-terminal hydrolase L1 (UCHL1) have been reported in the brains of sporadic Alzheimer's disease (AD) patients, and the introduction of UCHL1 rescued the synaptic and cognitive function of AD model mice. Obviously, a reduction in the levels of UCHL1 may play a role in the pathogenesis of AD. However, the mechanisms underlying the regulation of UCHL1 levels in AD have not been fully elucidated. ⋯ Furthermore, overexpression of microRNA-922 increased the phosphorylated tau levels. In conclusion, miR-922 increasing the levels of phosphorylated tau by regulating UCHL1 levels contributed to the pathogenesis of AD. Our study partly explained one of the mechanisms underlying the downregulation of UCHL1 levels in AD patients and could enrich the content of tau pathology in the pathogenesis of AD.
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Accumulating evidence supports that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase contributes to microglia-mediated neurotoxicity in the CNS neurodegenerative diseases. Several studies, including ours, suggest that microglial activation is involved in the retinal degeneration in the animal models of retinitis pigmentosa (RP). In the present study, we investigated the activation of NADPH oxidase in the rod degeneration in rd mice and further explored its role in the microglia-mediated photoreceptor apoptosis. ⋯ Apocynin markedly reduced the production of superoxide radicals and preserved the rod cells. The results suggested that NADPH oxidase might play an important role in the rod degeneration in the rd mice. Inhibition of NAPDH oxidase could be a possible approach to treat RP in the early degenerative stage.
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Encoding muscular force output during voluntary contractions is widely perceived to result, at least in part, from modulations in neuronal activity within the sensorimotor cortex. However the underlying electrophysiological phenomena associated with increased force output remains unclear. This study directly assessed sensorimotor cortex activity using electroencephalography (EEG) in humans performing isometric knee-extensions at a range of discrete torque levels. ⋯ Conversely, activity within the other frequency bands was not modulated by torque (P≥0.09), nor was overall CCD (P=0.11). Peripheral neuromuscular activation (quadriceps electromyography (EMG) amplitude) demonstrated distinct increases between each torque level (P<0.01). In conclusion, sensorimotor cortical activity within the gamma band demonstrated an overall increase with contraction torque, whereas both CCD and each of the other constituent frequency bands were not modulated by increments in torque magnitude during isometric knee-extension contractions up to 60%MVT.