Neuroscience
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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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Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions. ⋯ The NLRP3 KO mice displayed significantly moderated fatigue behaviors along with decreased PFC and serum IL-1β levels under the same treatment. These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment.
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are pathological pain-associated voltage-gated ion channels. They are widely expressed in central nervous system including spinal lamina II (also named the substantia gelatinosa, SG). Here, we examined the distribution of HCN channels in glutamatergic synaptic terminals as well as their role in the modulation of synaptic transmission in SG neurons from SD rats and glutamic acid decarboxylase-67 (GAD67)-GFP mice. ⋯ Consistently, forskolin (FSK) (an activator of adenylate cyclase) significantly increased the frequency of mEPSCs by 225±34%, which could be partially inhibited by ZD7288. Interestingly, the effects of ZD7288 and FSK on sEPSC frequency were replicated in non-GFP-expressing neurons, but not in GFP-expressing GABAergic SG neurons, in GAD67-GFP transgenic C57/BL6 mice. In summary, our results represent a previously unknown cellular mechanism by which presynaptic HCN channels, especially HCN4, regulate the glutamate release from presynaptic terminals that target excitatory, but not inhibitory SG interneurons.
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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.