The European journal of neuroscience
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Comparative Study
Shedding light on circadian clock resetting by dark exposure: differential effects between diurnal and nocturnal rodents.
The master circadian clock in mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, is entrained by light and behavioural stimulation. In addition, the SCN can be reset by dark pulses in nocturnal rodents under constant light conditions. Here, the shifting effects of a dark pulse on the SCN clock were detailed at both a behavioural and molecular level in a nocturnal rodent (Syrian hamster), and were compared to those of a diurnal rodent (Arvicanthis ansorgei). ⋯ Despite that both hamsters and Arvicanthis showed dark-induced phase advances at circadian time-12, Per1 gene and its protein PER1 were downregulated in Arvicanthis but not in hamsters. Altogether these results show that dark resetting of the SCN is always associated with downregulation of Per1 and/or Per2 expression, and mostly occurs during resting. Thus, the circadian window of sensitivity to dark differs between nocturnal and diurnal rodents.
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Nitric oxide (NO) and its synthesizing enzymes, including NO synthase-2 (NOS-2, also called inducible NOS, iNOS), have been implicated in spinal nociception. 1400W is a highly selective NOS-2 inhibitor, as compared with either NOS-1 (neuronal NOS, nNOS) or NOS-3 (endothelial NOS). Here we examined the anti-nociceptive effects of intrathecal (IT) administration of 1400W in two experimental models of hyperalgesia (formalin and carrageenan models), in addition to the effect of 1400W on stimulation-induced activation of spinal p38 mitogen-activated protein kinase (p38). IT treatment of rats with 1400W produced a dose-dependent inhibition of paw formalin-induced phase II flinches, and attenuated carrageenan-induced thermal hyperalgesia. ⋯ However, when the protein was immunoprecipitated prior to Western blotting, NOS-2-immunoreactive bands were detected in the tissues, including naïve spinal cords. The presence of constitutive spinal NOS-2 was further confirmed by reverse transcriptase-polymerase chain reaction. Taken together, the present studies suggest that constitutively expressed spinal NOS-2 mediates tissue injury and inflammation-induced hyperalgesia, and that activation of p38 is one of the downstream factors in NO-mediated signaling in the initial processing of spinal nociception.
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The absence of a slice preparation with intact thalamocortical pathways has held back elucidation of the cellular and synaptic mechanisms by which thalamic signals are differentially transmitted to and processed in the anterior cingulate cortex (ACC). In this report we introduce an innovative mouse brain slice preparation in which it is possible to explore the electrophysiological properties of ACC neurons with intact long-distance inputs from medial thalamic (MT) nuclei by intracellular recordings; this MT-ACC neuronal pathway plays an integral role in information transmission. Biocytin-labeled fibers in a functional slice could be traced anterogradely or retrogradely from the MT via the reticular thalamic nuclei, striatum and corpus callosum to the cingulate cortical areas. ⋯ We observed enhanced paired-pulse facilitation and tetanic potentiation of thalamocingulate synapses, suggestive of input-specific ACC plasticity and selective processing of information relayed by thalamocingulate pathways. Furthermore, we observed differential responses of ACC neurons to thalamic burst stimulation, which underscores the importance of MT afferents in relaying sensory information to the ACC. This new slice preparation enables the contribution of MT-evoked ACC synaptic transmission to short-term plasticity in the neuronal circuitry underlying sensory information processing to be examined in detail.
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Comparative Study
Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C.
Botulinum neurotoxin type A (BoNT/A) is commonly used in human therapy. This treatment may induce immunoresistance and preliminary evaluation of other botulinum neurotoxin serotypes suggested botulinum neurotoxin type C (BoNT/C) to be a good alternative to BoNT/A. Here, we have further characterized the biological activities of BoNT/C using a variety of experimental approaches. ⋯ In BoNT/C-treated junctions, nerve terminal sprouting was prominent, indicating that the capacity to extend the field of innervation is not hampered by BoNT/C. BoNT/C induced a marked decrease in the frequency of miniature endplate potentials and in the amplitude of endplate potentials. 3,4-diaminopyridine reversed the effect of BoNT/C by increasing the amplitude of synchronized endplate potentials. The present study shows an extensive similarity in the biological activities of BoNT/A and BoNT/C, further supporting the suggestion that BoNT/C is a valid alternative to BoNT/A.
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Transient receptor potential vanilloid (TRPV)1 is a ligand-gated cation channel expressed by primary sensory neurons, including those in the dorsal root ganglia (DRG). TRPV1 plays an essential role in development of inflammatory thermal hyperalgesia after tissue injury and its expression in rat lumbar DRG is increased after hindpaw inflammation. However, the identity of factors mediating forepaw inflammatory hyperalgesia has remained elusive. ⋯ Paratracheal injection of short interfering RNA targeting TRPV1 blocked TRPV1 up-regulation in cervical DRG and abolished inflammation-mediated HPL reductions seen at 50 degrees C. However, thermal hyperalgesia previously established by inflammation was not reversed by short interfering RNA injection. These results indicate that: (i) enhanced TRPV1 expression in cervical DRG is closely associated with development of inflammatory thermal hyperalgesia in the forepaw after tissue injury and (ii) RNA interference targeting TRPV1 prevents inflammatory thermal hyperalgesia after forepaw injuries but does not ameliorate it when already established in a rat model of nociceptive pain representing upper limb injury in humans.