Maternal exposure to hexachlorophene targets intermediate-stage progenitor cells in the hippocampal neurogenesis involving myelin vacuolation of cholinergic and glutamatergic inputs in mice.

Hexachlorophene (HCP) has been shown to induce myelin vacuolation due to intramyelinic edema of the nerve fibers in animal neural tissue. We investigated the maternal exposure effect of HCP on hippocampal neurogenesis in the offspring of pregnant mice supplemented with 0 (control), 33 or 100 ppm HCP in diet from gestational day 6 to day 21 after delivery. On postnatal day (PND) 21, offspring as examined in males exhibited decreased granule cell lineage populations expressing paired box 6, sex-determining region Y-box 2 and eomesodermin in the hippocampal subgranular zone (SGZ) accompanied by myelin vacuolation involving white matter tracts of the hippocampal fimbria at ≥ 33 ppm. However, SGZ cellular populations expressing brain lipid binding protein and doublecortin were unchanged at any dose. Transcript expression of cholinergic receptor genes, Chrna4 and Chrnb2, and glutamate receptor genes, Grm1 and Grin2d, examined at 100 ppm, decreased in the dentate gyrus. HCP exposure did not alter the number of proliferating or apoptotic cells in the SGZ, or reelin- or calcium-binding protein-expressing γ-aminobutyric acid (GABA)ergic interneurons in the dentate hilus, on PND 21 and PND 77. All neurogenesis-related changes observed in HCP-exposed offspring on PND 21 disappeared on PND 77, suggesting that maternal HCP exposure at ≥ 33 ppm reversibly decreased type 2 intermediate-stage progenitor cells in the hippocampal neurogenesis. Myelin vacuolation might be responsible for changes in neurogenesis possibly by reducing nerve conduction velocity of cholinergic inputs from the septal-hippocampal pathway to granule cell lineages and/or GABAergic interneurons, and of glutamatergic inputs to granule cell lineages.

Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice.

We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb)(+) γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2·xH2O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb(+) GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb(+) interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb.

Change in pulse wave velocity throughout normal pregnancy and its value in predicting pregnancy-induced hypertension: a longitudinal study.

OBJECTIVE: We longitudinally examined the changes of brachial to ankle distensibility using pulse wave velocity (PWV) throughout pregnancy and its difference between normal pregnancy and pregnancy-induced hypertension (PIH) groups. STUDY DESIGN: One hundred and eighty-three pregnant women were included in this study. The PWV examinations were performed in a longitudinal way during the first, second, and third trimesters of pregnancy, and immediately and 1 month after delivery. RESULTS: In normal pregnancies, the PWV significantly decreased at the second trimester, increased from the third trimester through immediately after delivery, and decreased again at 1 month after delivery. In PIH patients, it increased in proportion to the progression of gestation. CONCLUSION: We monitored the longitudinal changes in PWV and constructed a PWV normogram during pregnancy. The predictive value of PWV and blood pressure for PIH was higher than that of blood pressure alone, suggesting the usefulness of measuring PWV to predict PIH.

Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice.

We examined possible roles of mast cells in cutaneous wound healing using mast cell deficient (W/Wv) mice and their normal littermates (+/+). A round full-thickness wound was made on the back skin of these mice. The wounds closed completely within 20 days, and there was no difference in wound contraction between +/+ and W/Wv mice during the wound healing. While either chymase or tryptase activities were hardly detectable in W/Wv mice, chymase activities decreased at the impaired sites and recovered to the control level within 20 days in +/+ mice. Tryptase activities were higher than the control level on day 15 and day 20 in +/+ mice. Histological observations on day 15 and day 20 in +/+ mice revealed that mast cells were abundant at the wound edges but absent at the center. The latent and the active forms of MMP-2 and MMP-9 increased on day 10 and day 15 but recovered nearly to control levels on day 20 in both mice groups. The hydroxyproline contents in W/Wv mice were significantly higher than those in +/+ mice on day 15 and day 20. Furthermore, histological observations revealed that the collagen aggregation at the wound edges was tighter and less interwoven in W/Wv mice compared with +/+ mice. These results suggest that mast cells accumulated at the wound edge may participate in tissue remodeling in the late phase of wound healing.