Mediator Med23 Regulates Adult Hippocampal Neurogenesis.

Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.

Expression of DCX and Transcription Factor Profiling in Photothrombosis-Induced Focal Ischemia in Mice.

Adult neurogenesis is present in the dentate gyrus and the subventricular zone in mammalian brain under physiological conditions. Recently, adult neurogenesis has also been reported in other brain regions after brain injury. In this study, we established a focal striatal ischemic model in adult mice via photothrombosis (PT) and investigated how focal ischemia elicits neurogenesis in the striatum. We found that astrocytes and microglia increased in early post-ischemic stage, followed by a 1-week late-onset of doublecortin (DCX) expression in the striatum. The number of DCX-positive neurons reached the peak level at day 7, but they were still observed at day 28 post-ischemia. Moreover, Rbp-J (a key effector of Notch signaling) deletion in astrocytes has been reported to promote the neuron regeneration after brain ischemia, and we provided the change of gene expression profile in the striatum of astrocyte-specific Rbp-J knockout (KO) mice glial fibrillary acidic protein (GFAP-CreER:Rbp-Jfl/fl), which may help to clarify detailed potential mechanisms for the post-ischemic neurogenesis in the striatum.

Expression of transcription factor Satb2 in adult mouse brain.

Previous investigations on the expression and function of special AT-rich sequence binding protein 2 (Satb2) are largely limited to the cerebral cortex. Here, we explore the expression of Satb2 thoroughly by immunohistochemistry in the adult mouse central nervous system (CNS). Besides the cerebral cortex, we found that Satb2 is specifically expressed in the bed nucleus of the stria terminalis, horizontal limb of the diagonal band, lateral hypothalamic area, arcuate nucleus, hypothalamic paraventricular nucleus, ventral tegmental nucleus, laterodorsal tegmental nucleus, dorsal raphe nucleus, rostral periolivary region, and parabrachial nucleus. Double immunostaining showed that Satb2 is exclusively expressed in the excitatory neurons of neocortex. In addition, Satb2 is specifically expressed in A12 group of hypothalamic dopaminergic neurons and in serotonergic neurons in the dorsal part of the dorsal raphe nucleus. Our results present a comprehensive overview of Satb2 expression in the adult brain and provide insights for studying the role of Satb2 in the mature CNS.

[Polysomnographic findings and clinical presentation of adult men with obstructive sleep apnea].

AIM: To determine the age-related differences in the polysomnography (PSG) and clinical presentation of Chinese male adult subjects with obstructive sleep apnea (OSA), and attempt to identify the age-specific effects on the severity of sleep apnea. METHODS: This retrospective study included a cohort of 836 Chinese male a-dult subjects, who were diagnosed with OSA by the initial overnight PSG and recruited from the clinic population. The eligible subjects were classified into three different age groups: 312 young (mean 37. 07 years), 359 middle-aged(mean 52. 14 years) and 165 older (mean 69.43 years),and their polysomnographic findings and clinical presentation were assessed for the age-specific differences. RESULTS: The AHI-TST between the middle-aged and older subjects was similar (P > 0. 05), but less severe than the young(P <0.01). This trend was also observed in obstructive AI,AHI-NREM, and AHI-REM. The minimum SaO2 was higher in middle-aged and older subjects than in the young ones(P < 0.01). Central Al became greater following age in-crease (P <0.05). In sleep architecture, the elderly had lower total sleep time, sleep duration NREM or REM, and sleep efficiency than the younger (P < 0. 01), whereas sleep latency and WASO became longer ( P < 0. 01).Across all study population, age significantly correlated with AHI (P<0.01), obstructive Al (P<0.01), central AI (P<0.01) and minimum SaO2 ( P < 0. 01). Multiple regression analyses identified that age as an independent variable associated with AHI, obstructive Al and central Al respective- ly, after adjusting for confounding factors. CONCLUSION: In Chinese clinic subjects with OSA, age as an independent predictor associates with sleep apnea severity, presenting as decreased OSA and increased CSA with age.

Expression of the LIM-homeodomain gene Lmx1a in the postnatal mouse central nervous system.

The LIM-homeodomain transcription factor Lmx1a plays critical roles in roof plate formation as well as in the cell fate determination of midbrain dopaminergic neurons during embryonic development, but its function in the adult brain remains unknown. In the present study, as the first step in exploring its function in adult brain, we examined the expression of Lmx1a in the mouse central nervous system (CNS) from birth to adulthood by in situ hybridization. Lmx1a was expressed at high levels in the posterior hypothalamic area, supremammillary nucleus, ventral premammillary nucleus, subthalamic nucleus, ventral tegmental area, compact part of the substantia nigra and parabrachial nucleus from birth to adulthood, and co-localized with its paralogue Lmx1b in these regions. On the other hand, Lmx1a expression in the cochlear nuclei, medial cerebellar nucleus and superior vestibular nucleus was only observed until postnatal day (P) 30 and showed no colocalization with Lmx1b. Lmx1a-expressing neurons in the ventral midbrain were dopaminergic as evidenced by co-expression with tyrosine hydroxylase in these regions. Furthermore, Lmx1a expression was also found in the choroid plexuses and ependymal cells, although its expression was only detected during the first two postnatal weeks. These results suggest that Lmx1a may be involved in postnatal development as well as in maintenance of some aspects of normal brain function.

Expression of the transcription factor GATA3 in the postnatal mouse central nervous system.

GATA binding protein 3 (GATA3) is an important regulator of central nervous system (CNS) development, but its expression pattern in the postnatal CNS has not been studied. In the present study, we examined the distribution of GATA3 mRNA in the mouse CNS at different postnatal stages by in situ hybridization. During the first 2 weeks of postnatal development, numerous GATA3-expressing cells were found in the intergeniculate leaf, ventral lateral geniculate nucleus, pretectal nucleus, nucleus of the posterior commissure, superior colliculus, inferior colliculus, periaqueductal grey, substantia nigra and raphe nuclei. Few notable changes in the profile of GATA3 expression occurred over this time period. As postnatal development progressed, however, GATA3 expression weakened, and was maintained in only a few regions of the adult CNS. Throughout the brain, we found that GATA3-expressing cells were NeuN-positive, and no colocalization with glial fibrillary acidic protein (GFAP) was observed. In the substantia nigra, GATA3 was exclusively expressed in cells of the reticulate part and some of which were found to be GABAergic. This study presents a comprehensive overview of GATA3 expression in the CNS throughout postnatal life, and the dynamics that we observed provide insights for further investigations of the roles of GATA3 in postnatal development and the maintenance of the mature CNS.

Ultrastructure of junction areas between neurons and astrocytes in rat supraoptic nuclei.

AIM: To determine the ultrastructure of junction areas between neurons and astrocytes of supraoptic nuclei in rats orally administered 30 g/L NaCl solution for 5 days. METHODS: The anti-connexin (CX) 43 and anti-CX32 double immunoelectromicroscopic labeled method, and anti-Fos or anti-glial fibrillary acidic protein (GFAP) immunohistochemistry were used to detect changes in the junctional area between neurons and astrocytes in supraoptic nuclei of 5 rats after 30 g/L NaCL solution was given for 5days. RESULTS: A heterotypic connexin32/connexin43 gap junction (HGJ) between neurons and astrocytes (AS) in rat supraoptic nuclei was observed, which was characterized by the thickening and dark staining of cytomembranes with a narrow cleft between them. The number of HGJs and Fos like immunoreactive (-LI) cells was significantly increased following hyperosmotic stimuli, that is, the rats were administered 30 g/L NaCl solution orally or 90 g/L NaCl solution intravenously. HGJs could be blocked with carbenoxolone (CBX), a gap junction blocker, and the number of Fos-LI neurons was significantly decreased compared with that in rats without CBX injection, while Fos-LI ASs were not affected. CONCLUSION: HGJ may be a rapid adaptive signal structure between neurons and ASs in response to stimulation.

Two major distinct subpopulations of neurokinin-3 receptor-expressing neurons in the superficial dorsal horn of the rat spinal cord.

This study was designed to provide evidence for elucidating the mechanisms of neurokinin-3 receptor (NK3) in spinal pain modulation. First, colocalization of NK3 with the micro -opioid receptor (MOR1) was studied in the spinal dorsal horn of the rat. Confocal microscopy showed that about 44% of NK3-expressing neurons in laminae I and II were immunoreactive for MOR1, which corresponded to about 93% of the total population of MOR1-containing neurons in these laminae. Second, the relationship between NK3/MOR1-coexpressing neurons and those that express nitric oxide synthase (NOS) was examined by using a triple immunofluorescent staining method. About 37% of NK3-immunoreactive neurons were also NOS-immunoreactive, which constituted about 82% of NOS-immunoreacitve neurons in the superficial laminae. However, no triple-labelled neurons were detected. The present results indicate that there are two major distinct subpopulations of NK3-expressing neurons in the superficial dorsal horn, which suggests that the involvement of NK3 receptor in spinal nociception could be mediated by two distinct mechanisms, i.e. opioid and nitric oxide.