BRAIN and NERVE－神経研究の進歩70巻7号

2018年07月発行

増大特集 記憶と忘却に関わる脳のしくみ—分子機構から健忘の症候まで

軽運動による脳の活性化と記憶の増強

著者： 征矢英昭¹² 岡本正洋¹² 陸暲洙¹² 小泉光¹

所属機関： ¹筑波大学体育系運動生化学・神経内分泌学研究室 ²ヒューマン・ハイ・パフォーマンス先端研究センター・スポーツ神経科学研究室

ページ範囲：P.745 - P.752

文献概要

運動は海馬神経新生を促進し記憶能を向上させる。この最適条件を解明すべく，われわれは乳酸性作業閾値（LT）に基づいて強度を統制する運動モデルを確立した。これにより，ストレス応答を伴わないLT以下の低強度運動でも海馬神経は十分に活性化すること，慢性的な運動トレーニングにより神経新生促進と記憶能向上が生じることをつかんでいる。本論ではこれまで明らかにした低強度運動効果とそれを担う分子機構の一端について述べる。

参考文献

1)Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, et al: Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A 108: 3017-3022, 2011

2)Pereira AC, Huddleston DE, Brickman AM, Sosunov AA, Hen R, et al: An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci U S A 104: 5638-5643, 2007

3)Chaddock L, Erickson KI, Prakash RS, Kim JS, Voss MW, et al: A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children. Brain Res 1358: 172-183, 2010

4)Altman J, Das GD: Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124: 319-335, 1965

5)Zhang CL, Zou Y, He W, Gage FH, Evans RM: A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451: 1004-1007, 2008

6)Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, et al: Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci U S A 103: 17501-17506, 2006

7)Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, et al: Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472: 466-470, 2011

8)van Praag H, Kempermann G, Gage FH: Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266-270, 1999

9)van Praag H, Christie BR, Sejnowski TJ, Gage FH: Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 96: 13427-13431, 1999

10)van Praag H, Shubert T, Zhao C, Gage FH: Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25: 8680-8685, 2005

11)Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ: Running enhances spatial pattern separation in mice. Proc Natl Acad Sci U S A 107: 2367-2372, 2010

12)Soya H, Mukai A, Deocaris CC, Ohiwa N, Chang H, et al: Threshold-like pattern of neuronal activation in the hypothalamus during treadmill running: establishment of a minimum running stress (MRS) rat model. Neurosci Res 58: 341-348, 2007

13)Saito T, Soya H: Delineation of responsive AVP-containing neurons to running stress in the hypothalamus. Am J Physiol Regul Integr Comp Physiol 286: R484-R490, 2004

14)Soya H, Nakamura T, Deocaris CC, Kimpara A, Iimura M, et al: BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 358: 961-967, 2007

15)Girouard H, Iadecola C: Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985) 100: 328-335, 2006

16)Nishijima T, Soya H: Evidence of functional hyperemia in the rat hippocampus during mild treadmill running. Neurosci Res 54: 186-191, 2006

17)Nishijima T, Okamoto M, Matsui T, Kita I, Soya H: Hippocampal functional hyperemia mediated by NMDA receptor/NO signaling in rats during mild exercise. J Appl Physiol (1985) 112: 197-203, 2012

18)Chi OZ, Liu X, Weiss HR: Effects of inhibition of neuronal nitric oxide synthase on NMDA-induced changes in cerebral blood flow and oxygen consumption. Exp Brain Res 148: 256-260, 2003

19)Bhardwaj A, Northington FJ, Ichord RN, Hanley DF, Traystman RJ, et al: Characterization of ionotropic glutamate receptor-mediated nitric oxide production in vivo in rats. Stroke 28: 850-856; discussion 856-857, 1997

20)Mirescu C, Gould E: Stress and adult neurogenesis. Hippocampus 16: 233-238, 2006

21)Conrad CD: A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychiatry 34: 742-755, 2010

22)Inoue K, Okamoto M, Shibato J, Lee MC, Matsui T, et al: Long-term mild, rather than intense, exercise enhances adult hippocampal neurogenesis and greatly changes the transcriptomic profile of the hippocampus. PLOS ONE 10: e0128720, 2015［doi: 10.1371/journal.pone.0128720］

23)Inoue K, Hanaoka Y, Nishijima T, Okamoto M, Chang H, et al: Long-term mild exercise training enhances hippocampus-dependent memory in rats. Int J Sports Med 36: 280-285, 2015

24)Nishijima T, Piriz J, Duflot S, Fernandez AM, Gaitan G, et al: Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS. Neuron 67: 834-846, 2010

25)Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, et al: VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci 18: 2803-2812, 2003

26)Moon HY, Becke A, Berron D, Becker B, Sah N, et al: Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metab 24: 332-340, 2016

27)Russo-Neustadt AA, Alejandre H, Garcia C, Ivy AS, Chen MJ: Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology 29: 2189-2199, 2004

28)Vaynman S, Ying Z, Gomez-Pinilla F: Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20: 2580-2590, 2004

29)Yoshioka M, Boivin A, Ye P, Labrie F, St-Amand J: Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured by serial analysis of gene expression. J Mol Endocrinol 36: 247-259, 2006

30)MacLusky NJ, Hajszan T, Prange-Kiel J, Leranth C: Androgen modulation of hippocampal synaptic plasticity. Neuroscience 138: 957-965, 2006

31)Nguyen TV, Jayaraman A, Quaglino A, Pike CJ: Androgens selectively protect against apoptosis in hippocampal neurones. J Neuroendocrinol 22: 1013-1022, 2010

32)Okamoto M, Hojo Y, Inoue K, Matsui T, Kawato S, et al: Mild exercise increases dihydrotestosterone in hippocampus providing evidence for androgenic mediation of neurogenesis. Proc Natl Acad Sci U S A 109: 13100-13105, 2012

33)Okamoto M, Inoue K, Iwamura H, Terashima K, Soya H, et al: Reduction in paracrine Wnt3 factors during aging causes impaired adult neurogenesis. FASEB J 25: 3570-3582, 2011

34)Tronson NC, Taylor JR: Molecular mechanisms of memory reconsolidation. Nat Rev Neurosci 8: 262-275, 2007

35)Trent RJ, Yu B: The future of genetic research in exercise science and sports medicine. Med Sport Sci 54: 187-195, 2009

36)Vance JE, Hayashi H, Karten B: Cholesterol homeostasis in neurons and glial cells. Semin Cell Dev Biol 16: 193-212, 2005

37)Kimoto T, Tsurugizawa T, Ohta Y, Makino J, Tamura Ho, et al: Neurosteroid synthesis by cytochrome p450-containing systems localized in the rat brain hippocampal neurons: N-methyl-D-aspartate and calcium-dependent synthesis. Endocrinology 142: 3578-3589, 2001

38)Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, et al: A critical role for IGF-II in memory consolidation and enhancement. Nature 469: 491-497, 2011

39)Agis-Balboa RC, Arcos-Diaz D, Wittnam J, Govindarajan N, Blom K, et al: A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories. EMBO J 30: 4071-4083, 2011