Prenatal and Lactational Exposure to Bisphenol A in Mice Alters Expression of Genes Involved in Cortical Barrel Development without Morphological Changes

It has been reported that premature infants in neonatal intensive care units are exposed to a high rate of bisphenol A (BPA), an endocrine disrupting chemical. Our previous studies demonstrated that corticothalamic projection was disrupted by prenatal exposure to BPA, which persisted even in adult mice. We therefore analyzed whether prenatal and lactational exposure to low doses of BPA affected the formation of the cortical barrel, the barreloid of the thalamus, and the barrelette of the brainstem in terms of the histology and the expression of genes involved in the barrel development. Pregnant mice were injected subcutaneously with 20 µg/kg of BPA daily from embryonic day 0 (E0) to postnatal 3 weeks (P3W), while the control mice received a vehicle alone. The barrel, barreloid and barrelette of the adult mice were examined by cytochrome C oxidase (COX) staining. There were no significant differences in the total and septal areas and the patterning of the posterior medial barrel subfield (PMBSF), barreloid and barrelette, between the BPA-exposure and control groups in the adult mice. The developmental study at postnatal day 1 (PD1), PD4 and PD8 revealed that the cortical barrel vaguely appeared at PD4 and completely formed at PD8 in both groups. The expression pattern of some genes was spatiotemporally altered depending on the sex and the treatment. These results suggest that the trigeminal projection and the thalamic relay to the cortical barrel were spared after prenatal and lactational exposure to low doses of BPA, although prenatal exposure to BPA was previously shown to disrupt the corticothalamic projection

Structure and expression of two highly related genes encoding SCM-1/human lymphotactin

AbstractSCM-1/lymphotactin is a chemokine-like molecule produced selectively, if not exclusively, by activated CD8+ T cells. Here we report that there are two highly homologous SCM-1 genes, which we designate as SCM-1α and SCM-1β. Both genes have three exons and two introns. The 1st intron of SCM-1α contains a pseudogene of the ribosomal large subunit L7a. In SCM-1β, a 1.5-kb region including about a quarter of the L7a pseudogene is deleted from the 1st intron. Otherwise, the two genes are highly homologous including the 5′ and 3′ flanking regions. Both genes were mapped to human chromosome 1q23. The two genes were similarly induced in peripheral blood mononuclear cells by mitogenic stimulation. Primer extension and RNase protection revealed several transcription initiation sites. The biological activities of SCM-1α and SCM-1β, which have two amino acid differences at positions 7 and 8 in the mature proteins, remain to be compared

The Shortest Isoform of Dystrophin (Dp40) Interacts with a Group of Presynaptic Proteins to Form a Presumptive Novel Complex in the Mouse Brain

Duchenne muscular dystrophy (DMD) causes cognitive impairment in one third of the patients, although the underlying mechanisms remain to be elucidated. Recent studies showed that mutations in the distal part of the dystrophin gene correlate well with the cognitive impairment in DMD patients, which is attributed to Dp71. The study on the expression of the shortest isoform, Dp40, has not been possible due to the lack of an isoform specific antibody. Dp40 has the same promoter as that found in Dp71 and lacks the normal C-terminal end of Dp427. In the present study, we have raised polyclonal antibody against the N-terminal sequence common to short isoforms of dystrophin, including Dp40, and investigated the expression pattern of Dp40 in the mouse brain. Affinity chromatography with this antibody and the consecutive LC-MS/MS analysis on the interacting proteins revealed that Dp40 was abundantly expressed in synaptic vesicles and interacted with a group of presynaptic proteins, including syntaxin1A and SNAP25, which are involved in exocytosis of synaptic vesicles in neurons. We thus suggest that Dp40 may form a novel protein complex and play a crucial role in presynaptic function. Further studies on these aspects of Dp40 function might provide more insight into the molecular mechanisms of cognitive impairment found in patients with DMD

Changes of gene expression in developing mouse brain - A comparative study between exposure to carbon particles and to X-rays.

The 2nd International Workshop on Space Radiation Researc

Prenatal Low-dose X-irradiation Affects Connexins 43 and 26 in Developing Mouse Neocortex

To investigate the effects of low-dose X-irradiation on the expression of connexing(Cxs) in developing cerebral cortex, C57/BL6 pregnant mice were exposed to whole body irradiation of 0.1 Gy and 0.5Gy, on embryonic day 14.5 Fetal telencephalons, at 1,3,12 and 24 hr after exposure, were studied immunohistochemically using anti-Cx43 and Cx26 antibodies, followed by quantitative image analyses. Cx43 expression was significantly reduced in all zones of developing cerebal cortex antil 12hr after exposure,and tended to recover to control level after 24 hr. Cx26 expression was also suppressed in the ventricular zone and cortical p;ate after irradiation, although it recovered much earlier. Our observations indicate that the expression of Cxs is affected by ionizing radiation during cortical histogenesis

The Effects of Heavy Ion Particles on the Developing Murine Cerebellum, with Special Reference to Cell Death

We report here the effects of heavy ion beam on postnatal mouse cerebellar development, with reference to cell death. Eight-day-old B6C3F1 mice were irradiated with single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, using a carbon beam of 290 MeV/u delivered from a heavy ion medical accelerator in Chiba (HIMAC). To compare the effects of X-rays with those of accelerated carbon ions, 8-day-old mice were exposed to X-rays single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, respectively. Pups were fixed at 1, 6, 12 and 24 hr after exposure to HIMAC beams or X-rays. Four-mm-thick parasagittal sections of the cerebella were processed for staining with the TUNEL (terminal dUTP nick-end labeling) technique. The density of fragmented unclei in the external granular layer increased with time, peaking at 6 hr after exposure, in both the HIMAC and X-irradiated groups. In the HIMAC groups, the density was significantly higher in those animals exposed to 0.25 Gy or more compared to 0 Gy, whereas in the X-irradiated groups it was significantly higher in those mice exposed to 0.5 Gy or more. Electron microscopic ezaminations revealed chromatin condensation in the first in vivo evidence that aplptotic cell death is induced in developing mouse cerebellum after exposeure to heavy ion particles and to X-rays may reflect the high linear energy transfer (LET) associated with a heavy ion beam