Neuroscience
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Inflammation and pain are major clinical burdens contributing to multiple disorders and limiting the quality of life of patients. We previously reported that brain electrical stimulation can attenuate joint inflammation in experimental arthritis. Here, we report that non-aversive electrical stimulation of the locus coeruleus (LC), the paraventricular hypothalamic nucleus (PVN) or the ventrolateral column of the periaqueductal gray matter (vlPAG) decreases thermal pain sensitivity, knee inflammation and synovial neutrophilic infiltration in rats with intra-articular zymosan. ⋯ The duration of the tonic immobility increases the control of pain and inflammation. These results reveal survival behavioral and neuromodulatory mechanisms conserved in different species to control pain and inflammation in aversive life-threatening conditions. Our results also suggest that activation of the LC, PVN, or vlPAG by non-invasive methods, such as physical exercise, meditation, psychological interventions or placebo treatments may reduce pain and joint inflammation in arthritis without inducing motor or behavioral alterations.
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Vasogenic cerebral edema formation after blood-brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). The present study aims to probe into a therapeutic method on BBB preservation after ICH with a glycogen synthase kinase-3β (GSK-3β) inhibitor, lithium. Intrastriatal infusion of semicoagulated autologous whole blood or sham surgery was performed on male Sprague-Dawley (SD) rats (n = 208). ⋯ Expressions of Akt, GSK-3β, β-catenin, claudin-1 and claudin-3 were evaluated via Western blots. Our results showed lithium alone posttreatment activated GSK-3β, therefore increasing active β-catenin and claudin-1 and claudin-3 expressions, which were accompanied with improved BBB integrity and ameliorated sensorimotor deficits and brain edema in ICH animals. We concluded that lithium alone reduced BBB damage after ICH, likely through regulating Akt/GSK-3β pathway and stabilizing β-catenin.
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Recent studies investigating neural correlates of human thirst have identified various subcortical and telencephalic brain areas. The experience of thirst represents a homeostatic emotion and a state that slowly evolves over time. Therefore, the present study aims at systematically examining cerebral perfusion during the parametric progression of thirst. ⋯ However, significant differences across all four thirst stages (including the moderate thirst level), were exclusively found in the posterior insular cortex. The subjective thirst ratings over the different thirst stages, however, were associated with perfusion differences in the right anterior insula. These findings add to our understanding of the insular cortex as a key player in human thirst - both on the level of physiological dehydration and the level of the subjective thirst experience.
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Adenosine is a powerful modulator of skeletal neuromuscular transmission, operating via inhibitory or facilitatory purinergic-type P1 receptors. To date, studies have been focused mainly on the effect of adenosine on presynaptic P1 receptors controlling transmitter release. In this study, using two-microelectrode voltage-clamp and single-channel patch-clamp recording techniques, we have explored potential postsynaptic targets of adenosine and their modulatory effect on nicotinic acetylcholine receptor (nAChR)-mediated synaptic responses in adult mouse skeletal muscle fibers in vitro. ⋯ Using specific ligands for the P1 receptor subtypes, we found that the low-affinity P1 receptor subtype A2B was responsible for mediating the effects of adenosine on the nAChR channel openings. Our data suggest that at the adult mammalian NMJ, adenosine acts not only presynaptically to modulate acetylcholine transmitter release, but also at the postsynaptic level, to enhance the activity of nAChRs. Our findings open a new scenario in understanding of purinergic regulation of nAChR activity at the mammalian endplate region.
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Corticotropin-releasing factor receptors (CRFR1) contribute to stress-induced adaptations in hippocampal structure and function that can affect learning and memory processes. Our prior studies showed that female rats with elevated estrogens compared to males have more plasmalemmal CRFR1 in CA1 pyramidal cells, suggesting a greater sensitivity to stress. Here, we examined the distribution of hippocampal CRFR1 following chronic immobilization stress (CIS) in female and male rats using immuno-electron microscopy. ⋯ Moreover, after CIS, which leads to even greater sex differences in CRFR1 by trafficking it to different subcellular compartments, CRF could enhance activation of CA1 pyramidal cells in males but to a lesser extent than either unstressed or CIS females. Additionally, CA3 pyramidal cells and inhibitory interneurons in males have heightened sensitivity to CRF, regardless of stress state. These sex differences in CRFR1 distribution and trafficking in the hippocampus may contribute to reported sex differences in hippocampus-dependent learning processes in baseline conditions and following chronic stress.