Sex differentiation on the emotional and behavioral responses in mice

2008 Fiscal Year Final Research Report

• Project/Area Number: 16086204
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Azabu University (2007-2008); The University of Tokyo (2004-2006)
• Principal Investigator: KIKUSUI Takefumi Azabu University, 獣医学部, 准教授 (90302596)
• Project Period (FY): 2004 – 2008
• Keywords: 早期離乳 / BDNF / 胎生期 / アンドロゲン / 前頭葉

Research Abstract

早期離乳マウスのオス特異的な不安行動増強に並行して中枢ミエリン形成の早期化、前頭前野ならびに海馬BDNF発現量の低下、海馬歯状回における新生神経細胞数の低下がオス特異的に確認された。早期離乳マウスにBDNFを投与群することで不安行動が緩解したことから、BDNFの発現量の雌雄差が不安行動の差につながることが明らかとなった。次に、性ステロイドによる性差形成作用を調べたところ、胎生期14日目のマウスへのテストステロン投与により、メスのオス型の表現型の獲得が確認され、胎生期アンドロゲン暴露が性差を決定していることが示唆された。また脳の性差が多様な性分化メカニズムで形成され、またその性差が可塑的因子によって制御されていることが明らかとなってきた。

Research Products

• [Journal Article] Early weaning induces anxiety and precocious myelination in the anterior part of the basolateral amygdala of male Balb/c mice (2008)
  • Author(s): Ono, M., Kikusui T., Mori, Y. Ichikawa, M. Murofushi, K
  • Journal Title: Neuroscience 28 156(4) Pages: 1103-1110
• [Journal Article] Influence of pre- and postnatal early life environments on the inhibitory properties of familiar urine odors in male mouse aggression (2008)
  • Author(s): Nakamura K., Kikusui T., Takeuchi Y., Mori Y
  • Journal Title: Chem. Senses 33 Pages: 541-551
• [Journal Article] Effects of isolation rearing on the development of social behaviors in male Mongolian gerbils (Meriones unguiculatus) (2008)
  • Author(s): Shimozuru, M., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Physiol Behav 94 Pages: 491-500
• [Journal Article] Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female Wistar rats (2008)
  • Author(s): Kodama Y., Kikusui T., Takeuchi Y., Mori Y
  • Journal Title: Dev Psychobiol 50 Pages: 332-342
• [Journal Article] Enhancement of the acoustic startle reflex by an alarm pheromone in male rats (2008)
  • Author(s): Inagaki H. Kiyokawa Y, Kikusui T., Takeuchi Y., Mori Y
  • Journal Title: Physiol Behav 93 Pages: 606-611
• [Journal Article] Changes in social instigationand food restriction-induced aggressive behaviors and hippocampal 5HT1B mRNA receptor expression in male mice from early weaning (2008)
  • Author(s): Nakamura K., Kikusui T., Takeuchi Y., Mori Y
  • Journal Title: Behav. Brain Res 187 Pages: 442-448
• [Journal Article] Wheel-running activity increases with social stress in male DBA mice (2008)
  • Author(s): Uchiumi K., Aoki M., Kikusui T., Takeuchi Y., Mori Y
  • Journal Title: Physiol Behav 93 Pages: 1-7
• [Journal Article] Innate versus learned odor processing in the mouse olfactory bulb (2007)
  • Author(s): Kobayakawa K., Kobayakawa R., Matsumoto H., Oka Y., Imai T., Ikeda M., Itohara S., Ikawa M., Okabe M., Kikusui T., Mori K., Sakano H
  • Journal Title: Nature 450 Pages: 503-508
• [Journal Article] Alteration of behavioural phenotype in mice by targeted disruption of the progranulin gene (2007)
  • Author(s): Kayasuga Y., Chiba S., Suzuki M., Kikusui T., Matsuwaki T., Yamanouchi K., Kotaki H., Horai R., Iwakura Y., Nishihara M
  • Journal Title: Behav Brain Res 185 Pages: 110-118
• [Journal Article] Maternal approaches to pup ultrasonic vocalizations produced by a nanocrystalline silicon thermo-acoustic emitter (2007)
  • Author(s): Uematsu A., Kikusui T., Kihara T., Harada T., Kato M., Nakano K., Murakami O., Koshida N., Takeuchi Y., Mori Y
  • Journal Title: Brain Res 1163 Pages: 91-99
• [Journal Article] Fostering and environmental enrichment ameliorate anxious behavior induced by early weaning in Balb/c mice (2007)
  • Author(s): Iwata E., Kikusui T., Takeuchi Y., Mori Y.
  • Journal Title: Physiol Behav 91 Pages: 318-324
• [Journal Article] Early weaning decreases play-fighting behavior during the post-weaning developmental period of Wister rats (2007)
  • Author(s): Shimozuru, M., Kodama, Y., Iwasa, T., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Dev Psychobiol in press 49 Pages: 345-350
• [Journal Article] Discrimination of Individuals by Odor in Male Mongolian Gerbils, Meriones unguiculatus (2007)
  • Author(s): Shimozuru, M., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Zool Sci 24 Pages: 427-433
• [Journal Article] Removal of the vomeronasal organ blocks the stress-induced hyperthermia response to alarm pheromone in male rats (2007)
  • Author(s): Kiyokawa, Y., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Chem Senses 32(1) Pages: 57-64
• [Journal Article] The critical role of familiar urine odor in diminishing territorial aggression toward a castrated intruder in mice (2007)
  • Author(s): Nakamura, K., Kikusui, T., Takeuchi, Y. andMori, Y
  • Journal Title: Physiol Behav 90(2-3) Pages: 512-517
• [Journal Article] Deprivation of mother-pup interaction by early weaning alters myelin formation in male, but not female, ICR mice (2007)
  • Author(s): Kikusui, T., Kiyokawa, Y. and Mori, Y
  • Journal Title: Brain Res 1133(1) Pages: 115-122
• [Journal Article] Early weaning augments neuroendocrine stress responses in mice (2006)
  • Author(s): Kikusui, T., Nakamura, K., Kakuma, Y. and Mori, Y
  • Journal Title: Behav Brain Res 175(1) Pages: 96-103
• [Journal Article] Social-defeat stress suppresses scent-marking and social-approach behaviors in male Mongolian gerbils (Meriones unguiculatus) (2006)
  • Author(s): Shimozuru, M., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Physiol Behav 88(4-5) Pages: 620-7
• [Journal Article] Effects of early weaning on anxiety and autonomic responses to stress in rats (2006)
  • Author(s): Ito, A., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Behav Brain Res 171(1) Pages: 87-93
• [Journal Article] Reproduction of mouse-pup ultrasonic vocalizations by nanocrystalline silicon thermoacoustic emitter (2006)
  • Author(s): Kihara, T., Harada, T., Kato, M., Nakano, K., Murakami, O., Kikusui, T. and Koshida, N
  • Journal Title: Appl Phys Lett 88(4) Pages: 043902(1-3)
• [Journal Article] Alarm pheromone increases defensive and risk assessment behaviors in male rats (2006)
  • Author(s): Kiyokawa, Y., Shimozuru, M., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Physiol Behav 87(2) Pages: 383-387
• [Journal Article] Scent-marking and sexual activity may reflect social hierarchy among group-living male Mongolian gerbils (Meriones unguiculatus) (2006)
  • Author(s): Shimozuru, M., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Physiol Behav 89(5) Pages: 644-9
• [Journal Article] Mapping the neural circuit activated by alarm pheromone perception by c-Fos immunohistochemistry (2005)
  • Author(s): Kiyokawa, Y., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Brain Res 1043(1-2) Pages: 145-54
• [Journal Article] Social stress decreases marking behavior independently of testosterone in Mongolian gerbils (2005)
  • Author(s): Yamaguchi, H., Kikusui, T., Takeuchi, Y., Yoshimura, H. and Mori, Y
  • Journal Title: Horm Behav 47(5) Pages: 549-55
• [Journal Article] Repeated maternal separation : differences in cocaine-induced behavioral sensitization in adult male and female mice (2005)
  • Author(s): Kikusui, T., Faccidomo, S. and Miczek, K. A
  • Journal Title: Psychopharmacology 178(2-3) Pages: 202-210
• [Journal Article] Early weaning deprives mouse pups of maternal care and decreases their maternal behavior in adulthood (2005)
  • Author(s): Kikusui, T., Isaka, Y. and Mori, Y
  • Journal Title: Behav Brain Res 162(2) Pages: 200-6
• [Journal Article] Alarm pheromone that aggravates stress-induced hyperthermia is soluble in water (2005)
  • Author(s): Kiyokawa, Y., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Chem Senses 30(6) Pages: 513-9
• [Journal Article] The influence of social environmental condition on the production of stress-induced 22 kHz calls in adult male Wistar rats (2005)
  • Author(s): Inagaki, H., Kuwahara, M., Kikusui, T. and Tsubone, H
  • Journal Title: Physiol Behav 84(1) Pages: 17-22
• [Journal Article] Multidimensional structure of anxiety-related behavior in early-weaned rats (2005)
  • Author(s): Kanari, K., Kikusui, T., Takeuchi, Y. and Mori, Y
  • Journal Title: Behav Brain Res 156(1) Pages: 45-52
• [Journal Article] Brief social defeat stress : long lasting effects on cocaine taking during a binge and zif268 mRNA expression in the amygdala and prefrontal cortex (2005)
  • Author(s): Covington, H. E., 3rd, Kikusui, T., Goodhue, J., Nikulina, E. M., Hammer, R. P., Jr. and Miczek, K. A
  • Journal Title: Neuropsychopharmacology 30(2) Pages: 310-321
• [Journal Article] Behavioral and neurochemical consequences of early weaning in rodents
  • Author(s): Kikusui, T., Mori, Y.
  • Journal Title: J. Neuronedocrinol (in press)
• [Journal Article] Maternal deprivation by early weaning decreases hippocampal BDNF and neurogenesis in mice
  • Author(s): Kikusui, T., Ichikawa, S., Mori, Y.
  • Journal Title: Psychoneuronedocrinology (in press)
• [Journal Article] he volatility of an alarm pheromone in male rats
  • Author(s): Inagaki, H., Nakamura, K., Kiyokawa, Y., Kikusui, T., Takeuchi, Y., Mori, Y
  • Journal Title: Physiol. Behav (in press)
• [Journal Article] Dog's gaze at its owner increases owner's urinary oxytocin during social interaction
  • Author(s): Nagasawa, M. Kikusui, T., Onaka, T., Ohta, M
  • Journal Title: Horm. Behav (in press)
• [Presentation] Maternal deprivation by early weaning increases corticosterone and decreases hippocampal BDNF and neurogenesis in mice (2008)
  • Author(s): Kikusui, T. Ichikawa, S., Mori, Y
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-12
• [Presentation] Pre-and postnatal programming of familiar urine odors in malemice (2008)
  • Author(s): Kikusui, T
  • Organizer: 第6回国際シンポジウム「味覚嗅覚の分子神経機構」
  • Place of Presentation: 福岡
  • Year and Date: 20081206-07
• [Presentation] Early weaning augments anxiety and decreases BDNF protein levels in the pre-limbic system in male ICR mice (2008)
  • Author(s): Kikusui, T
  • Organizer: Strategies to Reduce Risks on the Brain Development Contingent to Urbanization
  • Place of Presentation: Tsukuba
  • Year and Date: 20081023-25
• [Presentation] Pre-and postnatal programming of familiar urine odors in male mice (2008)
  • Author(s): Kikusui, T. Nakamura, K
  • Organizer: UK-Japan Frontiers of Science Symposium
  • Place of Presentation: Shonan Village Center
  • Year and Date: 20081004-06
• [Presentation] 父性行動による早期離乳マウスの不安行動改善効果 (2008)
  • Author(s): 小島隼、菊水健史、武内ゆかり、森裕司
  • Organizer: 第146回日本獣医学会
  • Place of Presentation: 宮崎大学
  • Year and Date: 20080924-26
• [Presentation] Sex Differences in response to early weaning is reversed by prenatal androgen treatment (2008)
  • Author(s): Kikusui, T
  • Organizer: International Symposium for Sex Differentiation
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20080914-16
• [Presentation] Behavioral and neurochemical sex differences in response to early weaning (2008)
  • Author(s): Kikusui, T. Mori, Y
  • Organizer: US/JAPAN Neurosteroid SYMPOSIUM
  • Place of Presentation: Gifu, Japan
  • Year and Date: 20080908-11
• [Presentation] Sex difference in response to early weaning is reversed by prenatal androgen treatment (2008)
  • Author(s): Kikusui, T. Mori, Y
  • Organizer: US/JAPAN Neurosteroid SYMPOSIUM
  • Place of Presentation: Gifu, Japan
  • Year and Date: 20080908-11
• [Presentation] Behavioral and neurochemical changes induced by maternal deprivation in mice Frontiers of comparative cognitive developmental neuroscience (2008)
  • Author(s): Kikusui, T
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-09-13
• [Presentation] Maternal approaches to pup ultrasonic vocalizations produced by a nanocrystalline silicon thermo-acoustic emitter (2007)
  • Author(s): Kikusui T, Uematsu A, Takeuchi Y, Mori Y, Nakano Y, Murakami O, Kihara T, Harada T, Koshida N
  • Organizer: Society for Neuroscience 37th annual meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071103-07
• [Presentation] Two types of social buffering effects on conditioned fear responses in male rats (2007)
  • Author(s): Kiyokawa Y, Takeuchi Y, Mori Y
  • Organizer: ociety for Neuroscience 37th annual meeting San Diego
  • Place of Presentation: USA
  • Year and Date: 20071103-07
• [Presentation] Behavioral adaptation using chemical cues in rodents (2007)
  • Author(s): Kikusui T
  • Organizer: Asia-Pacific Conference on Chemical Ecology 2007 Symposium B Sociobiology and human
  • Place of Presentation: Tsukuba
  • Year and Date: 20070911-13
• [Presentation] 早期離乳によるマウスのストレス内分泌軸の持続的活性化 (2007)
  • Author(s): 市川創造,菊水健史,武内ゆかり,森裕司
  • Organizer: 第144回日本獣医学会学術集会
  • Place of Presentation: 北海道江別市
  • Year and Date: 20070902-04
• [Presentation] 早期離乳による行動および神経系の変容 (2007)
  • Author(s): 菊水健史
  • Organizer: 第143回日本獣医学会学術集会日本獣医解剖学会シンポジウムII「脳のストレス応答」
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 20070403-05
• [Presentation] 川上賞受賞講演「早期離乳ストレスに対する雌雄差の解析とステロイドホルモンの関与」 (2006)
  • Author(s): 菊水健史
  • Organizer: 第33回日本神経内分泌学会学術集会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 20061027-28
• [Presentation] エソロジーからみた社会行動の基盤研究 (2006)
  • Author(s): 菊水健史
  • Organizer: 日本動物心理学会第66回大会ワークショップ「日本における行動神経内分泌研究の動向」
  • Place of Presentation: 京都府京都市
  • Year and Date: 20061013-15
• [Presentation] ラットにおける早期離乳による社会的遊び行動の現象と不安傾向の増大 (2006)
  • Author(s): 岩佐高志,菊水健史,武内ゆかり,森裕司
  • Organizer: 日本動物心理学会第66回大会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20061013-15
• [Presentation] ICRマウスにおける新奇環境下での行動及び内分泌反応の雌雄差検討 (2006)
  • Author(s): 青木麻実,菊水健史,武内ゆかり,森裕司
  • Organizer: 日本動物心理学会第66回大会
  • Place of Presentation: 京都府京都市京都大学百周年時計台記念館
  • Year and Date: 20061013-15
• [Presentation] マウスにおける社会的親和・回避行動に関する研究. (2006)
  • Author(s): 内海香織,青木麻実,菊水健史,武内ゆかり,森裕司
  • Organizer: 日本動物心理学会第66回大会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20061013-15
• [Presentation] マウス雌雄における仔マウス超音波に対する反応性の相違 (2006)
  • Author(s): 植松朗,菊水健史,武内ゆかり,森裕司
  • Organizer: 日本動物心理学会第66回大会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20061013-15
• [Presentation] Behavioral adaptation using social cues in rodents (2006)
  • Author(s): Kikusui T
  • Organizer: International Symposium on Social Cognition as Higher Brain Function, Keio University
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20060801-03
• [Presentation] Early weaning arguments anxiety and decrease BDNF protein levels in the pre-limbic system in male ICR mice (2006)
  • Author(s): 菊水健史,森裕司
  • Organizer: 第29回日本神経科学大会
  • Place of Presentation: 京都府京都市
  • Year and Date: 20060719-21
• [Presentation] Sex differences in the early weaning-induced augmentation of anxiety and decrease of BDNF protein levels in the re-limbic system in ICR mice (2006)
  • Author(s): Kikusui T, Mori Y
  • Organizer: Society of Behavioral Neuroendocrinology 10 th Annual Meeting
  • Place of Presentation: Pittsburgh,U.S.A
  • Year and Date: 20060617-20
• [Presentation] Early weaning increases anxiety and decreases play fighting behavior in rats (2006)
  • Author(s): Shimozuru M, Kodama Y, Iwasa T, Kikusui T, Takeuchi Y, Mori Y
  • Organizer: Society of Behavioral Neuroendocrinology 10 th Annual Meeting
  • Place of Presentation: Pittsburgh, U.S.A,
  • Year and Date: 20060617-20
• [Presentation] 一般シンポジウム「予想的環境認知の神経機構-社会的行動の成り立ちに関する生理学的研究」 (2006)
  • Author(s): 菊水健史
  • Organizer: 第83回日本生理学会大会
  • Place of Presentation: 群馬県前橋市
  • Year and Date: 20060328-30
• [Presentation] シンポジウム(生理学・生化学分科会)「幼少期社会環境が情動行動と脳の発達に及ぼす影響」 (2006)
  • Author(s): 菊水健史,森裕司
  • Organizer: 第141回日本獣医学会学術集会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 20060319-21
• [Presentation] 早期離乳操作がラットの行動と脳の発達に及ぼす影響 (2006)
  • Author(s): 兒玉有加,菊水健史,武内ゆかり,森裕司
  • Organizer: 第141回日本獣医学会学術集会
  • Place of Presentation: 茨城県つくば市 つくば国際会議場
  • Year and Date: 20060319-21
• [Remarks] ホームページ等
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