母子分離ストレスが報酬探索行動に及ぼす影響と側坐核におけるドーパミンD1受容体のDNAのメチル化機構を介した発現変化について

Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual’s life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS + SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS + SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS + SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MS + SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region.博士（医学）・甲第672号・平成29年6月28日Copyright © 2017 Elsevier B.V. All rights reserved

骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.博士（医学）・甲第656号・平成28年11月24日© Copyright 2016 American Association of Neurological SurgeonsThe definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250

カレイ ニ トモナウ ケッショウα-トコフェロール ノウド ノ ヘンドウ

加齢に伴い血漿中のα-トコフェロール濃度が上昇するかどうか、男子23名(年齢16〜63才)、女子13名(年齢24〜61才)の血漿中のa-トコフェロール濃度をHPLC法で測定した。その結果、男子では加齢に伴いα-トコフェロール濃度が上昇するという正の相関が得られた(y=0.179 x +4.684,r=0.626)。女子では加齢に伴いα-トコフェロール濃度が変化するという明確な結論は得られなかった。岡山県S村往民(男子309名、女子361名)のビタミンEの摂取量を年齢別にみたが、E摂取量は年齢が70才より高くなるに従い男女とも低下する傾向が認められた。血漿中のα-トコフェロール濃度の上昇が、肝臓中a-トコフェロール濃度の減少により生じた可能性を検討するために、24ヶ月齢の老齢ラットと3ヶ月齢の若齢ラット(Wistar系雄)の血漿および肝臓中のα-トコフェロール濃度を比較した。ラットもヒト男性と同様、加齢に伴い血漿α-トコフェロール濃度は有意に上昇し、肝臓や脾臓も有意なα-トコフェロール濃度の増加が認められた。これらの結果、加齢に伴う男子の血漿中α-トコフェロール濃度の上昇は肝臓などの臓器中濃度の低下により生じた可能性は少ないものと考えられる

オカヤマケン ニオケル ケンコウヅクリ ノタメノ セイカツ チョウサ ニ カイハツ シタ Microsoft Excel オ モチイル カンイ ショクモツ セッシュ ヒンド チョウサホウ

著者らは「岡山県の健康づくりのための生活調査」の簡易食物摂取調査のための, 半定量的食物摂取頻度調査法を開発した。この資料では誰でも容易に調査法が改良できるようにするため, この調査法の構成と計算の方法を示した。計算はMicrosoft社の表計算ソフトであるExcelで行った。そのため, 各カラムごとの計算を全て知ることができ, 調査法の改良がより容易になったものと推察される