Neuroscience
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Here we investigated effects of intramuscular (i.m.) heating-needle stimulation on persistent muscle nociception evoked by i.m. injection of different doses (50-200 µl) of complete Freund's adjuvant (CFA) in rats. Paw withdrawal reflexes evoked by noxious mechanical and heat stimulation as well as hind limb swelling were determined prior to and two weeks after the CFA injection. The unilateral injection of CFA induced a dose-related and long-lasting (5-14 d), bilateral secondary mechanical hyperalgesia and heat hypoalgesia associated with long-term limb swelling. ⋯ In contrast, the hind limb swelling was not affected by the microinjection of A-317491 into the thalamic VM or MD nucleus. The present study indicates that in the CFA-induced persistent muscle nociception condition, 43 °C heating-needle stimulation selectively increases descending inhibition, which effect is modulated by the thalamic VM nucleus. In addition to the antinociceptive role of P2X3 receptors in the thalamic VM nucleus, P2X3 receptors within the thalamic MD nucleus participate in the descending facilitation evoked by i.m. 46 °C heating-needle stimulation.
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Peripheral neurostimulation within the trigeminal nerve territory has been used for pain alleviation during migraine attacks, but the mechanistic basis of this non-invasive intervention is still poorly understood. In this study, we investigated the therapeutic role of peripheral stimulation of the trigeminal nerve, which provides homosegmental innervation to intracranial structures, by assessing analgesic effects in a nitroglycerin (NTG)-induced rat model of migraine. As a result of neurogenic inflammatory responses in the trigeminal nervous system, plasma protein extravasation was induced in facial skin by applying noxious stimulation to the dura mater. ⋯ The results indicated that facial territories and intracranial structures were directly connected with each other through bifurcated double-labeled neurons in the TG and through second-order WDR neurons. Homotopic stimulation at the C-fiber intensity threshold resulted in much stronger inhibition of analgesia than the same intensity of heterotopic stimulation. These results provide novel evidence for the neurological bases through which peripheral neurostimulation may be effective in treating migraine in clinical practice.
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Sleep loss or insomnia is among the contributing factors of cognitive deficit, the underlying mechanisms of which remain largely elusive. The endocannabinoid (eCB) system plays a role in sleep, while it is unknown if it is involved in the regulation of memory retrieval by sleep deprivation. In addition, it still controversial how rapid-eye-movement sleep deprivation (REMSD) affects the spatial memory of adolescent mice. ⋯ Mechanistically, REMSD induced eCB-mediated short-term and long-term synaptic plasticity changing including depolarization-induced suppression of inhibition (DSI) in the pyramidal neurons of the hippocampus, in which long-term synaptic plasticity changing was rescued by NESS0327. REMSD downregulated monoacylglycerol lipase, a hydrolase for the endocannabinoid 2-arachidonoylglycerol (2-AG), suggesting the involvement of eCB accumulation and the consequent synaptic plasticity in REMSD-elicited memory impairment in adolescent mice. These findings shed light on the role of sleep disorders in learning and memory deficit of adolescents.
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In this study, we investigated the potential role of C-X-C chemokine receptor type (CXCR) 5 in neurocognitive function in a mouse model of sepsis-associated encephalopathy (SAE). Adult male C57BL/6J mice received intracerebroventricular injections of small interfering RNAs (siRNAs) against CXCR5 or scrambled control siRNA. After 3 days, SAE was induced by cecal ligation and puncture (CLP, n = 16 per group). ⋯ This was accompanied by increased expression of CXCR5, IL-1β and IL-6 in the hippocampus. CXCR5 knockdown attenuated the memory and learning deficits induced by CLP and partially reversed the effects of CLP on numbers of proliferating, immature and mature neurons, and on expression of IL-1β and IL-6 in the hippocampus. These results suggest that CXCR5 knockdown can attenuate sepsis-induced deficits in hippocampal neurogenesis and cognitive function in mice with SAE.
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Causal factors of psychiatric diseases are unclear, due to gene × environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DAT-KO), has enhanced our understanding into the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). ⋯ When comparing both MAT- and MIX-HET to WT-control rats, decreased levels of DAT and HDAC4 were evident in the ventral-striatum; moreover, with respect to MIX-HET subjects, MAT-HET ones displayed increased DAT density in dorsal-striatum. MAT-HET rats displayed region-specific changes in DAT expression, compared to "classical" MIX-HET subjects: greater DAT availability may elevate threshold for dopamine action. Further behavioral and epigenetic characterizations of MAT-HETs, together with deeper characterization of maternal roles, could help to explore parent-of-origin mechanisms for such a peculiar phenotype.