Neuroscience
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Glycosphingolipids (GSLs) are abundant, ceramide-containing lipids in the nervous system that play key functional roles in pain and inflammation. We measured gene expression (Ugcg, St3gal5, St8sia1, B4galNT1, Ugt8a, and Gal3st1) of glycosyltransferases involved in GSL synthesis in murine dorsal root ganglion (DRG) and spinal cord after complete Freund's adjuvant (CFA)-induced unilateral hind-paw inflammation (1 day vs. 15 days). Chronic inflammation (15 days) sensitized both ipsilateral and contralateral paws to pain. ⋯ Since intrathecal injection of b-series ganglioside induced mechanical allodynia in naïve mice, it seems reasonable that b-series gangliosides synthesized from upregulated St8sia1 in the ipsilateral spinal cord are involved in mechanical allodynia. By contrast, chronic inflammation led to a decrease of Ugcg, St3gal5, B4galnt1, and Gal3st1 expression in spinal cord bilaterally and an increase of St8sia1 expression in the ipsilateral DRG, suggesting that a-/b-series gangliosides in the spinal cord decreased and b-series gangliosides in ipsilateral DRG increased. These changes in glycosyltransferase gene expression in the DRG and the spinal cord may contribute to the modification of pain sensitivity in both inflamed and non-inflamed tissues and the transition from early to chronic inflammatory pain.
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Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Compared to traditional high-intensity, low-frequency (<100 Hz) SCS that is thought to produce paresthesia and pain relief by stimulating large myelinated fibers in the dorsal column (DC), low-intensity, high-frequency (10 kHz) SCS has demonstrated long-term pain relief without generation of paresthesia. ⋯ By using in vivo and ex vivo electrophysiological approaches, we found that low-intensity (sub-sensory threshold) 10 kHz SCS, but not 1 kHz or 5 kHz SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief.
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Mechanisms of Impulsive Responding to Temporally Predictable Events as Revealed by Electromyography.
Temporal predictability optimises behaviour when a simple response is required, as demonstrated by faster reaction times (RTs) and higher accuracy. However, its beneficial effects come at a cost under situations of response conflict. Here, we investigated the motor underpinnings of behaviour to temporally predictable events in the Simon conflict task. ⋯ There was, however, no effect of temporal predictability on subsequent suppression of partial errors. Our results provide direct evidence that temporal predictability acts by increasing the urge to initiate a fast, yet potentially erroneous, response. This mechanism parsimoniously explains both beneficial effects of temporal predictability when no conflict in the environment is present, as well as its costs when more complex motor behaviour is required.
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Maternal deprivation (MD) in rodents is used to simulate human-infant early life stress, which leads to neural, hormonal, and behavioral alterations. Palatable food (PF) can reduce the stress response, and individuals use it as a self-applied stress relief method. Thus, the present study aimed to evaluate the effect of the association between MD in the early life (P1-P10) and PF consumption (condensed milk, P21-P44) in the central neuroplasticity (BDNF/NGF levels) and central neuroinflammatory parameters (TNF-α, IL-6, and IL-10 levels) in male and female Wistar rats in the adolescence. ⋯ In conclusion, there were more noticeable effects of MD than PF on the variables measured in this study. Sex effect was identified as an important factor and influenced most of the neurochemical measures in this study. In this way, we suggest including both female and male animals in researches to improve the quality of translational studies.
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Circular RNAs are an increasingly important topic in non-coding RNA biology, drawing considerable attention in recent years. Accumulating evidence suggests a critical role for circular RNAs in both early and latent stages of disease pathogenesis. ⋯ Disruption of these processes, including those seen in response to brain injury, can have serious consequences such as hemiplegia, aphasia, coma, and death. In this review, we describe the role of circular RNAs in the context of brain injury and explore the potential connection between circular RNAs, brain hypoxic ischemic injury, ischemia-reperfusion injury, and traumatic injury.