更年期障害 http://www.jsog.or.jp/PDF/61/6107-238.pdf 女性ホルモンの分泌の低下により、女性ホルモンによる青斑核ノルアドレナリン・ニューロン発火の抑制がとれ、青斑核が興奮した状態と考えられる。 更年期障害の症状は熱感，のぼせ，心悸亢進，発汗，不眠などを中心とした自律神経失調症状と、不安感，抑鬱，恐怖感，疲労感などが中心の精神神経症状の2つに分けられる。これらは、青斑核の活動性で容易に説明できる。 産褥期精神障害 分娩後3〜10日頃に、妊娠中高値の女性ホルモンは、５０分の１のレベルまで低下する。女性ホルモンによる青斑核ノルアドレナリン・ニューロン発火の抑制がとれ、青斑核が興奮し、不安、不眠、情緒障害、気分の低下などが出現する。ほとんどが自然軽快するが、このマタニティブルーが産褥期うつ病に移行することもある。 | https://www.is.tohoku.ac.jp/information/pdf/2005/project2005-itoi.pdf 東北大学大学院情報科学研究科 （１） 学際的研究プロジェクト支援経費 実績報告書 タ イ ト ル 緑色蛍光タンパク発現トランスジェニック・マウスを用いた脳機能解析－青斑核ノルアドレナリン・ニューロンへの直視下パッチ・クランプ法の導入 （２）主 催 者 井樋慶一（情報科学研究科システム情報科学専攻） 坪川 宏（情報科学研究科応用情報科学専攻） （３）目 的 緑色蛍光タンパク（GFP）発現トランスジェニック・マウスを用い、青斑核ノルアドレナリン・ニューロンへの直視下パッチ・クランプ法を導入する。この方法を用い、緑色蛍光タンパク発現トランスジェニック・マウスを用いた脳機能解析－青斑核ノルアドレナリン・ニューロンのホルモンやペプチド応答性を検討する。 （４）内 容 カテコールアミン合成律速酵素であるチロシン水酸化酵素プロモーターにより GFP を発現させたトランスジェニック・マウスを用いた。青斑核を含む脳切片を用い、直視下で単一神経発火を記録した。女性ホルモンにより青斑核ノルアドレナリン・ニューロン発火が抑制される現象を世界に先駆けて発見した。 （５）情報科学研究科にとっての意義 ・ 貢 献 度 発生工学的手法（井樋）と電気生理学的手法（坪川）の学際的共同研究により、世界ではじめて、脳内ノルアドレナリン・ニューロンを直視下で同定しながら、電気現象の観察をおこなうことに成功した。今回開発された先駆的技術を応用することにより、脳内ルアドレナリン・ニューロンの機能解析が格段に進むものと考えられる。これらの成果は、国内外の学会で報告し、国際誌に投稿予定である。 J Neuroendocrinol. 2010 May;22(5):355-61. The brainstem noradrenergic systems in stress, anxiety and depression. Itoi K, Sugimoto N. The locus coeruleus (LC) is regarded as a part of the central 'stress circuitry' because robust activation of the LC has been reported after stressful stimuli in experimental animals. A considerable amount of clinical evidence also suggests the relationship between the central noradrenergic (NAergic) system and fear/anxiety states or depression. However, previous animal studies have not been able to demonstrate unequivocally the involvement of the NAergic system in mediating fear or anxiety. The forebrain structures, including the hypothalamus, receive massive inputs from the medullary NAergic nuclei via the ventral NAergic bundle (VNAB). The VNAB has been implicated in the neuroendocrine stress axis mainly through its action on the corticotrophin-releasing factor neurones in the paraventricular nucleus of the hypothalamus. Novel tools were introduced that are capable of disrupting the NAergic system more selectively and/or thoroughly than the neurotoxins employed in previous studies: the anti-dopamine-beta hydroxylase (DBH)-saporin is an immunotoxin that is taken up from nerve endings and disrupt the NAergic neurones in a retrograde manner. The genetically DBH-depleted mice were also introduced, which lack endogenous noradrenaline. Owing to the rapid development of functional imaging technique, visualisation of the emotional phenomena has become possible in human subjects. Along with the advent of these technologies, endeavors have been continued to unravel the functional relevance of the central NAergic system to stress, anxiety and depression. Psychopharmacol Bull. 1997;33(2):229-33. The influence of estrogen on monoamine oxidase activity. Chakravorty SG, Halbreich U. The enzyme monoamine oxidase (MAO) has generated considerable interest as a biological marker. The serendipitous discovery that iproniazid was a weak MAO inhibitor (MAOI) led to the development and widespread use of MAOIs as antidepressants in the early 1950s. The-discovery of the two isoenzymes of MAO has led to the development of selective MAOIs that may have a more favorable side-effect profile. The regulation of MAO is multifactorial, and there is evidence that it involves estrogens. Improvement in mood and cognition reported in women on estrogen replacement therapy may also involve changes in MAO activity. The literature in this regard is reviewed here, and possible implications of the effects of estrogens on MAO activity are discussed. Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system. Shughrue PJ, Lane MV, Merchenthaler I. J Comp Neurol. 1997 Dec 1;388(4):507-25. Estrogen plays a profound role in regulating the structure and function of many neuronal systems in the adult rat brain. The actions of estrogen were thought to be mediated by a single nuclear estrogen receptor (ER) until the recent cloning of a novel ER (ER-β). To ascertain which ER is involved in the regulation of different brain regions, the present study compared the distribution of the classical (ER-α) and novel (ER-β) forms of ER mRNA-expressing neurons in the central nervous system (CNS) of the rat with in situ hybridization histochemistry. Female rat brain, spinal cord, and eyes were frozen, and cryostat sections were collected on slides, hybridized with [35S]-labeled antisense riboprobes complimentary to ER-α or ER-β mRNA, stringently washed, and opposed to emulsion. The results of these studies revealed the presence of ER-α and ER-β mRNA throughout the rostral-caudal extent of the brain and spinal cord. Neurons of the olfactory bulb, supraoptic, paraventricular, suprachiasmatic, and tuberal hypothalamic nuclei, zona incerta, ventral tegmental area, cerebellum (Purkinje cells), laminae III–V, VIII, and IX of the spinal cord, and pineal gland contained exclusively ER-β mRNA. In contrast, only ER-α hybridization signal was seen in the ventromedial hypothalamic nucleus and subfornical organ. Perikarya in other brain regions, including the bed nucleus of the stria terminalis, medial and cortical amygdaloid nuclei, preoptic area, lateral habenula, periaqueductal gray, parabrachial nucleus, locus ceruleus, nucleus of the solitary tract, spinal trigeminal nucleus and superficial laminae of the spinal cord, contained both forms of ER mRNA. Although the cerebral cortex and hippocampus contained both ER mRNAs, the hybridization signal for ER-α mRNA was very weak compared with ER-β mRNA. The results of these in situ hybridization studies provide detailed information about the distribution of ER-α and ER-β mRNAs in the rat CNS. In addition, this comparative study provides evidence that the region-specific expression of ER-α, ER-β, or both may be important in determining the physiological responses of neuronal populations to estrogen action. |