Runt-related transcription factors (Runx) regulate the development of various cells. It has been reported that Runx1 and Runx3 are expressed in distinct subpopulations of primary sensory neurons in the dorsal root ganglion (DRG), and play important roles in the differentiation of nociceptive and proprioceptive neurons, respectively. In the present study, we examined the developmental changes of the expression of Runx1 and Runx3 in the mouse DRG during embryonic and postnatal stages. We found that the expression of Runx3 preceded that of Runx1, but dramatically decreased before birth, whereas the Runx1 expression was maintained during postnatal periods. These results suggest that roles of Runx1 and Runx3 may change dynamically in the differentiation and maturation of DRG neurons. In addition, several DRG neurons expressed both Runx1 and Runx3 throughout embryonic and postnatal stages and many Runx3-expressing DRG neurons coexpressed Runx1 at postnatal day 28. Double and triple labeling studies suggest that some of the Runx1/Runx3-double expressing neurons coexpressed TrkB, c-ret, and TrkC, which have been shown in the mechanoreceptive DRG neurons. These results suggest that Runx1/Runx3-double expressing neurons may represent mechanoreceptive properties in the DRG
The purpose of the present study was to examine the current situation regarding sedative (mainly benzodiazepines)-related disorder in Japan and the clinical characteristics of Japanese patients with this disorder.
The present study sought to determine whether the co-occurrence of problem drinking heightens suicide risk in individuals with depression in Japan, using a sample of 784 outpatients (287 men and 497 women) with depressive disorder. Female subjects with at least a moderate problem drinking showed significantly more severe depression and suicidality than those without, but no such difference was identified in men.
Transcription factor Runx1 controls the cell type specification of peptidergic and nonpeptidergic nociceptive dorsal root ganglion (DRG) neurons by repressing TrkA and calcitonin gene-related peptide (CGRP) expression and activating Ret expression during late embryonic and early postnatal periods (Chen et al., 2006b; Kramer et al., 2006; Yoshikawa et al., 2007). Because Runx1 is expressed in DRG from early developmental stages, we examined the roles of Runx1 in the proliferation and the neuronal differentiation of DRG cells. We used transgenic Runx1-deficient (Runx1(-/-)::Tg) mice which are rescued from early embryonic lethality by selective expression of Runx1 in hematopoietic cells under the control of GATA-1 promoter. We found that TrkA-expressing (TrkA(+)) DRG neurons were decreased at embryonic day (E) 12.5 in contrast to the previous study showing that TrkA(+) DRG neurons were increased at E17.5 in Runx1(-/-)::Tg mice (Yoshikawa et al., 2007). The number of DRG neurons which express neuronal markers Hu, NeuN and Islet1 was also reduced in Runx1(-/-)::Tg mice at E12.5, suggesting that the neuronal differentiation was suppressed in these mice. The cell cycle analysis using BrdU/IDU revealed that the number of DRG cells in S-phase and G2/M-phase was increased in Runx1(-/-)::Tg mice at E12.5, while the length of S-phase was not changed between Runx1(+/+)::Tg and Runx1(-/-)::Tg mice, suggesting that Runx1 negatively controls the proliferation of DRG progenitor cell subpopulation in early embryonic period. Hes1 is a negative regulator of neuronal differentiation (Ishibashi et al., 1995; Tomita et al., 1996), and we found that the number of Hes1(+) DRG cells was increased in Runx1(-/-)::Tg mice at E12.5. In summary, the present study suggests a novel function that Runx1 activates the neuronal differentiation of DRG cell subpopulation through the repression of Hes1 expression in early embryonic period.
The duration of the extracellular action potential (EAP) in single neuronal recording has often been used as a clue to infer biochemical, physiological or functional substrate of the recorded neurons, e.g. neurochemical type. However, when recording a neuronal activity, the high-pass filter is routinely used to achieve higher signal-to-noise ratio. Signal processing theory predicts that passband limitation stretches the waveform of discrete brief impulse. To examine whether the duration of filtered EAP could be the reliable measure, we investigated the influence of high-pass filter both by simulation and unfiltered unit recording data from monkey dorsal raphe. Consistent with the findings in recent theoretical study, the unfiltered EAPs displayed the sharp wave without following bumps. The duration of unfiltered EAP was not correlated with that of filtered EAP. Thus the duration of original EAP cannot be estimated from filtered EAP. It is needed to reexamine the EAP duration measured for classifying the neurons whose activities were recorded under the passband limitation in the related studies.
During development, the rescue of spinal motoneurons as well as sensory neurons in the dorsal root ganglion (DRG) from programmed cell death (PCD) depends on the integrity of peripheral target innervation. Following deletion of the pro-apoptotic gene Bax, both motoneurons and DRG neurons are rescued from PCD. In the present paper, we asked whether different cell types in the DRG exhibit distinct responses to Bax deletion. In 1-month-old Bax-deficient (Bax-/-) mice, distinct subsets of DRG neurons that were immunopositive for TrkA, CGRP, TRPV1 or TrkC, were all increased in number and exhibited cell atrophy compared to wild type DRG neurons. In addition there was hyperinnervation of the epidermis by CGRP immunopositive processes and a correlated functional hypersensitivity of mechanical nociception in Bax-/- mice. By contrast, the functional properties of populations of rescued thermoreceptor and mechanoreceptor DRG neurons were unchanged. These data indicate that although Bax deletion rescues all of the DRG cell types examined here from PCD, the functional consequences of having excess cells differ between sensory phenotypes.
Sensory neurons project axons to specific peripheral and central targets according to their sensory modality. Runx3 is crucially involved in proprioceptive dorsal root ganglion neuron development. Runx3 is also expressed in trigeminal ganglion (TG) neurons. The role of Runx3 in the TG, however, is largely unknown because the TG does not contain proprioceptive neurons. In Runx3-deficient (Runx3(-/-)) mice, TrkB-expressing TG neurons were increased, whereas TrkC-expressing TG neurons were decreased during TG neuron development. In Runx3(-/-) neonatal mice, TrkC-expressing TG neurons did not project to the Merkel cells in the outer root sheath (ORS) of whisker vibrissae peripherally and the spinal trigeminal nucleus pars interpolaris (Sp5I) centrally. These findings suggest that Runx3 is required for the specification of TrkC-expressing TG neurons, conveying mechanoreceptive signals from the Merkel cells in the ORS of the whisker vibrissae to the Sp5I.
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