Jae Bong Kim

Profile of Fos-like immunoreactivity induction by light stimuli in the intergeniculate leaflet is different from that of the suprachiasmatic nucleus.

Light stimuli induce Fos-like immunoreactivity (FLI) in suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL). Short pulses of light stimuli that synchronize the circadian rhythms induce FLI in SCN. The characteristics of light induction of FLI in the IGL were studied using immunohistochemistry. In the IGL, at least 2 h of sustained light stimuli were necessary to show an increase of FLI. This FLI persisted while the light was turned on. FLI induction in the IGL by light stimuli was not circadian time specific response. These findings imply that the functional significance of Fos activation on circadian rhythms and mechanism of FLI induction in IGL would be different from that in SCN.

Distributional characteristics of the mRNA for retinoid Z receptor β (RZRβ), a putative nuclear melatonin receptor, in the rat brain and spinal cord

We investigated the distribution of retinoid Z receptor beta (RZR beta), a putative nuclear melatonin receptor, mRNA in the rat brain and spinal cord using in situ hybridization. The RZR beta riboprobe uniquely hybridized with the neurons in several sensory pathways including the dorsal horn of the spinal cord, whereas the regions involved in the motor control were generally unlabeled. RZR beta mRNA was also highly expressed in the dorsomedial portion of the suprachiasmatic nucleus, pars tuberalis and some limbic areas. This result suggests that RZR beta plays a specific role as a transcription factor in the sensory, neuroendocrine and limbic systems.

Developmental expression of ‘RZRβ, a putative nuclear-melatonin receptor’ mRNA in the suprachiasmatic nucleus of the rat

RZR beta is a member of the retinoid Z receptor (RZR) family of orphan receptors, and its expression is brain-specific. Recently, it was reported that the distribution of RZR beta mRNA is partially coincident with melatonin binding sites and that RZR beta is a putative nuclear receptor of melatonin. Using in situ hybridization, we investigated the developmental expression of RZR beta mRNA in the suprachiasmatic nucleus (SCN) of the rat, which is considered as circadian pacemaker. The RZR beta mRNA was first found in the dorsomedial portion of the SCN at embryonic day 20, and RZR beta mRNA expression in the dorsomedial SCN continued until postnatal day 60. This result suggests that RZR beta plays specific roles as a transcription factor in the dorsomedial SCN but not in the ventrolateral SCN during development and throughout postnatal life.

Calcitonin gene-related peptide-like immunoreactive (CGRPI) elements in the circadian system of the mouse: an immunohistochemistry combined with retrograde transport study.

This study was based on immunohistochemical detection of calcitonin gene-related peptide-like immunoreactive (CGRPI) neurons and fibers in the suprachiasmatic nucleus (SCN) and intergeniculate leaflet (IGL) of the mouse. CGRPI neurons and fibers were found within the ventrolateral part of the SCN, in the whole extent of IGL and sparsely distributed in ventral lateral geniculate body. The presence of CGRPI structures in the SCN and IGL of the mouse further supports the hypothesis of differences in the content of neuroactive substances in the circadian clock between mammalian species. Fluorogold retrograde transport combined with CGRP immunofluorescence demonstrates that CGRPI neurons in the IGL constitute a part of IGL reciprocal connections.

RANKL stimulates proliferation, adhesion and IL-7 expression of thymic epithelial cells

In many clinical situations which cause thymic involution and thereby result in immune deficiency, T cells are the most often affected, leading to a prolonged deficiency of T cells. Since only the thymic-dependent T cell production pathway secures stable regeneration of fully mature T cells, seeking strategies to enhance thymic regeneration should be a key step in developing therapeutic methods for the treatment of these significant clinical problems. This study clearly shows that receptor activator of NF-κB ligand (RANKL) stimulates mouse thymic epithelial cell activities including cell proliferation, thymocyte adhesion to thymic epithelial cells, and the expression of cell death regulatory genes favoring cell survival, cell adhesion molecules such as ICAM-1 and VCAM-1, and thymopoietic factors including IL-7. Importantly, RANKL exhibited a significant capability to facilitate thymic regeneration in mice. In addition, this study demonstrates that RANKL acts directly on the thymus to activate thymus regeneration regardless of its potential influences on thymic regeneration through an indirect or systemic effect. In light of this, the present study provides a greater insight into the development of novel therapeutic strategies for effective thymus repopulation using RANKL in the design of therapies for many clinical conditions in which immune reconstitution is required.

Wnt7b is Upregulated in Macrophages during Thymic Regeneration and Negatively Regulated by RANKL

Thymus can regenerate to its normal mass within 14 days after acute involution induced by cyclophosphamide (CY) in adult rat. Despite the established role of Wnt pathways in the process of thymus development, they have not yet been associated with the regeneration of adult thymus. The purpose of this study was to investigate whether Wnt7b, which is expressed in developing thymic epithelial cells rather than in thymocytes, is modulated during thymic regeneration in adult rat. Here, we show that Wnt7b expression was up-regulated in the regenerating thymus. Cells immunolabeled for the Wnt7b were identified as macrophages. Furthermore, Wnt7b gene expression was decreased by the treatment of receptor activator of NF-kappaB ligand (RANKL). Taken together, our results demonstrate that Wnt7b gene expression was increased in macrophages during thymic regeneration and negatively regulated by RANKL.