Neuroscience
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We previously measured the time courses of hydrogen peroxide (H2O2), hydroxyl radical (*OH), and catalytic iron increases following traumatic spinal cord injury (SCI). This study determines whether the SCI-elevated level of *OH causes cell death. OH was generated by administering H2O2 and Fe2+ at the concentrations attained following SCI, each through a separate microdialysis fiber inserted laterally into the gray matter of the cord. ⋯ It also reduced the numbers of TUNEL-positive neurons (P=0.01). Electron microscopy confirmed that generated *OH induced neuronal and glial death with characteristic features of both necrosis and apoptosis. We conclude that 1) SCI-elevated *OH is sufficient to induce both necrosis and apoptosis, criteria for identifying an endogenous secondary damaging agent; 2) MnTBAP reduces *OH-induced cell death, perhaps by removing H2O2 administered in the tissue, thereby blocking formation of *OH, and also by scavenging downstream reactive species.
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Comparative Study
Detection and mapping of quantitative trait loci that determine responsiveness of mice to nitrous oxide antinociception.
Exposure to 70% N(2)O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N(2)O. Offspring from the F(2) generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N(2)O antinociception as determined by the acetic acid-induced abdominal constriction test. ⋯ Combined results revealed two significant QTL that influence responsiveness to nitrous oxide on proximal chromosome 2 and distal chromosome 5, and one suggestive QTL on midchromosome 18. The chromosome 2 QTL was evident only in males. A significant interaction was found between a locus on chromosome 6 and another on chromosome 13 with a substantial effect on N(2)O antinociception.
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Comparative Study
Altered expression of potassium channel subunit mRNA and alpha-dendrotoxin sensitivity of potassium currents in rat dorsal root ganglion neurons after axotomy.
Previous studies have raised the possibility that a decrease in voltage-gated K+ currents may contribute to hyperexcitability of injured dorsal root ganglion (DRG) neurons and the emergence of neuropathic pain. We examined the effects of axotomy on mRNA levels for various Kv1 family subunits and voltage-gated K+ currents in L4-L5 DRG neurons from sham-operated and sciatic nerve-transected rats. RNase protection assay revealed that Kv1.1 and Kv 1.2 mRNAs are highly abundant while Kv1.3, Kv1.4, Kv1.5 and Kv1.6 mRNAs were detected at lower levels in L4-L5 DRGs from sham and intact rats. ⋯ Axotomy decreased both types of K+ currents by 50-60% in injured DRG neurons. In addition, axotomy increased the alpha-dendrotoxin sensitivity of the delayed rectifier, but not slow A-type K+ currents in injured DRG neurons. These results suggest that Kv1.1 and Kv1.2 subunits are major components of voltage-gated K+ channels in L4-L5 DRG neurons and that the decreased expression of Kv1-family subunits significantly contributes to the reduction and altered kinetics of Kv current in axotomized neurons.
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Emotional self-regulation plays a pivotal role in socialization and moral development. This capacity critically depends on the development of the prefrontal cortex (PFC). The present functional magnetic resonance imaging study was conducted to identify the neural circuitry underlying voluntary self-regulation of sadness in healthy girls (aged 8-10). ⋯ Significant loci of activations were also detected in the right anterior cingulate cortex (BA 24/32) and right ventrolateral PFC (BA 47). In an identical study previously conducted by our group in adult women [Biol Psychiatry 53 (2003) 502], reappraisal of sad film excerpts was associated with activation of the right OFC (BA 11) and right LPFC (BA 9). The greater number of prefrontal loci of activation found in children relative to adults during voluntary self-regulation of sadness may be related to the immaturity of the prefronto-limbic connections in childhood.
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We previously demonstrated that spinal protein kinase C (PKC) is involved in the development of a neuropathic pain-like state induced by sciatic nerve ligation, and the morphine-induced rewarding effect is attenuated by sciatic nerve ligation in rodents. Here we first investigated whether sciatic nerve injury could change the activity of a conventional PKC (cPKC) and an atypical PKC isoform PKCzeta in the mouse spinal cord. The second experiment was to investigate whether direct inhibition of spinal PKC by intrathecal (i.t.) administration of a specific PKC inhibitor, 2-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indole-3-yl)maleimide (RO-32-0432), could affect the rewarding effect induced by morphine following sciatic nerve ligation in mice. ⋯ In the present study, we confirmed that the morphine-induced place preference was significantly suppressed by sciatic nerve ligation. It should be mentioned that i.t. pretreatment with RO-32-0432 significantly reversed the attenuation of morphine-induced rewarding effect following sciatic nerve ligation. These results suggest that activation of PKCs, including cPKC and PKCzeta, within the spinal cord is directly responsible for the attenuation of the morphine-induced rewarding effect under a neuropathic pain-like state following sciatic nerve ligation in mice.