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脳由来神経栄養因子（BDNF）の役割と運動の影響
健 康 科 学 Vol.31, 2009 年 3 月 −総 説− 脳由来神経栄養因子（BDNF）の役割と運動の影響 野藤 悠 1) ，諏訪雅貴 2) ，佐々木 悠 3) ，熊谷秋三 3)* The role of brain-derived neurotrophic factor (BDNF) and the effects of exercise Yu NOFUJI 1) , Masataka SUWA 2) , Haruka SASAKI and Shuzo KUMAGAI 3)* 3) , Abstract Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors and found in the nervous system and periphery. BDNF is known to promote the growth, development, maintenance of functions, and survival of the neuronal system. In addition, accumulating evidences suggest that BDNF may play important roles in memory, learning, mood disorder, food intake, and energy metabolism. Recently, decreased level of BDNF in the brain and blood has been reported in the patients with depression or Alzheimer ’s disease. On the other hand, exercise increased the expression of brain BDNF and its receptor (high-affinity tyrosine protein kinase receptor; TrkB), which mediated the improvement of memory and learning in rodents. Moreover, administration of BDNF to the diabetic obese mice suppressed the weight gain and improved the glucose metabolism. Those evidences raise the possibility that exercise contributes to the prevention or improvement of dementia, depression and diabetes through BDNF-trkB pathway. In this paper, we summarized the functions of BDNF and also reviewed the effects of exercise on BDNF especially focused on the circulating BDNF. Key words: brain-derived neurotophic factor, exercise, metabolism, depression (Journal of Health Science, Kyushu University, 31:49-59, 2009) 1）九州大学人間環境学府博士課程 Graduate school of Human-Environment Studies, Kyushu University 2）東北工業大学ライフデザイン学部 Faculty of Life Design, Tohoku Institute of Technology 3）九州大学健康科学センター Institute of Health Science, Kyushu University *連絡先：九州大学健康科学センター 〒816-8580 福岡県春日市春日公園 6-1 Tel&Fax：092-583-7853 *Correspondence to: Institute of Health Science, Kyushu University 6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580, Japan Tel&Fax: +81-92-583-7853 E-mail: [email protected] ஜ ᐽ ⑼ ቇ ╙ 31 Ꮞ 50 1. ߪ ߓ ߦ 3.$&0( ߩ ↢ ℂ ↪ ㄭᐕ, 2 ဳ♧ዩ∛, ⢈ḩ, ࡔ࠲ࡏ࠶ࠢࠪࡦ࠼ࡠ ಽ ᴲ ᕈ ࠲ ࡦ ࡄ ࠢ ⾰ ߪ ౝ ಽ ᴲ (endocrine), ற ಽ ᴲ ࡓߦઍߐࠇࠆ↢ᵴ⠌ᘠ∛ߩෂ㒾࿃ሶ߿߁ߟ, (paracrine), ⥄ Ꮖ ಽ ᴲ (autocrine)ߩ 3 ߟ ߩ ಽ ᴲ ᭽ ᑼ ⍮ ∝ ߥ ߤ ߩ ♖ ∔ ᖚ ߩ Ⴧ ട ߇ ක ≮␠ ળ 㗴 ߣ ࠍߣࠆߎߣ߇⍮ࠄࠇߡࠆ߇, ⚻ᩕ㙃࿃ሶߩಽ ߥߞߡࠆ৻ޕᣇߢ, ᣣᏱ⊛ߥㆇേߩ⛮⛯߇ 2 ဳ ᴲ߅ࠃ߮↪ᯏᐨߪறಽᴲ߅ࠃ߮⥄Ꮖಽᴲߢ ♧ዩ∛ 1)2) ߿ࠕ࡞࠷ࡂࠗࡑ∛ 3)4) ߩ⊒∝੍㒐߿∛ ࠅ, ↢ℂ⊛᧦ઙਅߢߪறಽᴲ߇ਥᵹߢࠆ ޕ ᘒᡷༀߦലᨐ⊛ߦߊߎߣ߽ࠄ߆ߦߐࠇߟߟ BDNF ߪ , ࠆߒ߆ߒޕ, ߘߩಽሶࡔࠞ࠾࠭ࡓߪචಽߦߪ⸃ protein kinase receptor; TrkB)ߣ 㜞 ⷫ ᕈ ߦ ⚿ ว ߒ , ߐࠇߡࠆߣߪ⸒㔍ޕ ⚦⢩ౝߩࠪࠣ࠽࡞વ㆐♽ࠍߒߡ, ߘߩ↢ℂ↪ ⣖ ↱ ᧪ ⚻ ᩕ 㙃 ࿃ ሶ㧔 brain-derived neurotrophic ࠍ⊒ើߔࠆ factor; BDNF㧕ߪ ⚻ ⚦ ⢩ ߩ ⊒ ↢ ߿ ᚑ 㐳 , ⛽ ᜬ , ୃ ౝ ߦ ߅ ߌ ࠆ ⚻ ࿁ 〝 ✂ ߩ ᒻ ᚑ ߿ ⊒ ㆐ 㧘↢ ሽ ߦ ㊀ ⷐ 5)6)7)8) ߘ ߩ ฃ ኈ (high-affinity 18) 5)19) tyrosine ޕ1990 ᐕ ઍ ߦ ߥ ߞ ߡ BDNF ߇ ⣖ , ߐࠄߦቇ⠌߿⸥ᙘ, ᖱേ, ៨㘩, ߢ ࠆ ߎ ߣ 㧘 ߐ ࠄ ߦ BDNF ߪ ࠪ ࠽ ࡊ ࠬ ߩ น ႟ ᕈ ♧ઍ⻢ߥߤߦ߅ߡ߽㊀ⷐߥ߈ࠍߔࠆಽᴲ࠲ (plasticity) ߦ ߽ 㑐 ਈ ߒ 㧘 ⸥ ᙘ ߿ ቇ ⠌ ߩ ᒻ ᚑ ߦ ߅ ࡦ ࡄ ࠢ ⾰ ߢ ࠆ ޕㄭ ᐕ , ߎ ߩ BDNF ߩ ⊒ ㊂ ߇ ߁ ߡ㊀ⷐߥᓎഀࠍᨐߚߒߡࠆߎߣ߇ࠄ߆ߦߥ ᓳߦ߈ ߟ∛ 9 ) 1 0 ) 11 ) ߿ࠕ࡞࠷ࡂࠗࡑ∛ᖚ⠪ 12) ߩ ⣖㧔 ਥ ߣ ߞߚ 20) ޕㄭᐕߢߪ, ߐࠄߦᖱേߩࠦࡦ࠻ࡠ࡞, ߒ ߡ ᶏ 㚍 㧘ᄢ ⣖ ⊹ ⾰ 㧕ߢ ᷫ ዋ ߒ ߡ ࠆ ߎ ߣ ߇ ⏕ ៨㘩ⴕേߩᛥ, ♧ઍ⻢ߦߊߥߤ, ᄙጘߦᷰߞ ߐ ࠇ ߡ ࠆ ৻ ޕᣇ , ㆇ േ ߇ ⣖ ౝ ߩ BDNF ࠍ Ⴧ ട ߐ ߚ↢ℂ↪߇ႎ๔ߐࠇߡࠆ 16)21)22)23) ޕ ߖࠆߣߣ߽ߦ, ቇ⠌߿⸥ᙘߩࡄࡈࠜࡑࡦࠬࠍᡷ ༀߐߖࠆߎߣ߽േ‛ታ㛎ߦࠃࠅႎ๔ߐࠇߡࠆ 13)14) ߚ ߹ ޕ, BDNF ࠍ ⣖ ቶ ౝ ࠆ ߪ ⊹ ਅ ߿ ⣻ ⣧ ౝߦᛩਈߔࠆߎߣߦࠃࠅ, ㊀ߩჇട߇ᛥߐࠇ, ♧ઍ⻢߇ᡷༀߐࠇࠆߎߣ߽ႎ๔ߐࠇߡࠆ 15)16) ޕ 1㧕 ⸥ ᙘ ቇ ⠌ ߩ ଦ ㅴ BDNF ߪ , ⸥ ᙘ ᒻ ᚑ ߩ ႐ ᚲ ߣ ߒ ߡ ⍮ ࠄ ࠇ ߡ ࠆ ᶏ㚍ߦ㜞Ớᐲሽߒߡ߅ࠅ 24)25) , ߘߩၮᧄ⊛ߥ ߈߆ࠄ߽ቇ⠌߿⸥ᙘߦ㑐ㅪߒߡࠆߣ⠨߃ࠄ ߎ ࠇ ࠄ ߩ ᚑ ❣ ߪ , ㆇ േ ߇ BDNF ⊒ ㅴ ࠍ ଦ ߔ ߎ ࠇ ߡ ߈ ߚ ޕ⣖ ౝ ߩ BDNF ⊒ ߇ ㊁ ↢ ဳ ࡑ ࠙ ࠬ ߦ Ყ ߣߦࠃࠅ, ⍮∝߿߁ߟ∛, ߐࠄߦߪ⢈ḩ∝߿♧ ߴ ⚂ ඨ ಽ ߢ ࠆ BDNF ࡋ ࠹ ࡠ ࡁ ࠶ ࠢ ࠕ ࠙ ࠻ ࡑ ࠙ ࠬ ዩ∛ߩ⊒∝੍㒐߿∛ᘒᡷༀߦ⽸₂ߒ߁ࠆߎߣࠍ ߢߪ, ቇ⠌⢻ജ߇ૐ୯ࠍ␜ߔߎߣ߇, ⓨ㑆⍮ߩ ␜ໂߒߡࠆޕ ⸥ᙘቇ⠌⢻ജࠍ⹏ଔߔࠆ᳓ㅅ〝⺖㗴ߦࠃߞߡ⏕ ᧄ Ⓜ ߢ ߪ , BDNF ߩ ↢ ℂ ⊛ ᓎ ഀ ࠍ ㅀ ߴ , ߐ ࠄ ߦ ߐࠇߡࠆ BDNF ߦ ߷ ߔ ㆇ േ ߩ ᓇ 㗀 ߦ ߟ ߡ , ․ ߦ ㆇ േ ⽶ 㔍႐ᚲߣߒߡ᳓㕙ਅߦ㓝ࠇߚบࠍ⟎߈, ࠶࠻ࠍ ⩄ ߦ ߁ ⴊ ਛ BDNF ߩ േ ᘒ ߦ ὶ ὐ ࠍ ߡ ߡ ⺑ ߔ ߔߣ, ⹜ⴕ࿁ᢙࠍ㊀ߨࠆ߁ߜߦ࿐ߩⷞⷡ⊛ߥ ࠆޕ ᚻដ߆ࠅࠍ߽ߣߦㆱ㔍႐ᚲࠍᙘ߃, ᣧߊบߦ㆐ 26) ޕ᳓ㅅ〝⺖㗴ߣߪ, ࡊ࡞ߦㆱ ߔࠆࠃ߁ߦߥࠆߣ߁߽ߩߢ 27) , ߎߩ᳓ㅅ〝ߩ 2. $&0( ߣ ߪ ᚑ ❣ ߣ ᶏ 㚍 ߦ ߅ ߌ ࠆ BDNFmRNA ⊒ ㊂ ߣ ߩ 㑆 ߦ ⚻ ᩕ 㙃 ࿃ ሶ (Neurotrophin) ߣ ߪ ⚻ ⚦ ⢩ ߩ ⊒ ᱜߩ⋧㑐㑐ଥ߇ႎ๔ߐࠇߡࠆ ↢ᚑ㐳⛽ ᜬౣ ↢ ࠍ ଦㅴ ߐ ߖ ࠆ ‛⾰ ߩ ✚ ⒓ ߢ ᛫ ࠍ ⣖ ቶ ౝ ߦ ᛩ ਈ ߒ , BDNF㧙 TrkB ࠪ ࠣ ࠽ ࡞ વ ࠅ, ߎࠇ߹ߢߦ᭽ߥޘᩕ㙃࿃ሶ߇หቯߐࠇߡ ㆐⚻〝ࠍਇᵴൻߔࠆߣߎߣߢ, ⸥ᙘ߿ቇ⠌㓚ኂࠍ ࠆ ⚻ ޕᩕ 㙃 ࿃ ሶ ߣ ߒ ߡ ᦨ ೋ ߦ ⊒ ߐ ࠇ ߚ ߩ ߪ ߊߎߣ߽⏕ߐࠇߡࠆ ⚻ ᚑ 㐳 ࿃ ሶ㧔 nerve growth factor; NGF; 1951㧕ߢ ࠄ , ᶏ 㚍 㗔 ၞ ߩ BDNF ߪ ቇ ⠌ ߿ ⸥ ᙘ ߦ ߅ ߡ ㊀ ⷐ ࠅ㧔 ⊒ ⠪ ߩ Levi-Montalchini ࠄ ߪ 1986 ᐕ ߦ ࡁ ߥᓎഀࠍᨐߚߒߡࠆߣ⠨߃ࠄࠇߡࠆޕ 29)30) 28) ߚ ߹ ޕ, BDNF ߩ ࠄ ࠇ ߎޕᚑ ❣ ߆ ࡌ ࡞ ක ቇ ↢ ℂ ቇ ⾨ ࠍ ฃ ⾨ 㧕, ᰴ ߢ 1982 ᐕ ߦ NGF ߣㄭ✼ߩㆮવሶ↥‛ߣߒߡ⣖↱᧪⚻ᩕ㙃࿃ሶ 㧔 BDNF㧕 ߇ Brade ࠄ 17) ߦࠃߞߡࡉ࠲ߩ⣖߆ࠄන 2㧕 ៨ 㘩 BDNF ߣ ߘ ߩ ฃ ኈ ߢ ࠆ TrkB ߪ , ៨ 㘩 ⴕ േ 31) ޕ 㔌 , ♖ ߐ ࠇ ߚ ޕBDNF ߪ , ಽ ሶ ㊂ 13.5kD, ࠕ ࡒ ߩਛᨔߢࠆⷞᐥਅㇱߦ߽⊒ߒߡࠆ ࡁ ㉄ 119 ࠃ ࠅ ߥ ࠆ ಽ ᴲ ᕈ ࠲ ࡦ ࡄ ࠢ ⾰ ߢ ࠅ , ࡎ BDNF ࡋ ࠹ ࡠ ࡁ ࠶ ࠢ ࠕ ࠙ ࠻ ࡑ ࠙ ࠬ ߢ ߪ ᣧ ᦼ ߆ ࠄ ㆊ ࡕ 2 ㊂ (homodimer)ߣ ߒ ߡ ሽ ߒ ߡ ࠆ ޕ 㘩ߣߣ߽ߦ㗼⪺ߥ㊀Ⴧട߇ࠄࠇࠆ߇ 32) , ⣖↱᧪⚻ᩕ㙃࿃ሶ㧔BDNF㧕ߩᓎഀߣㆇേߩᓇ㗀 ߎ ߩ ៨ 㘩 ⴕ േ ⇣ Ᏹ ߪ BDNF ࠍ ⣖ ቶ ߦ ᛩ ਈ ߔ ࠆ ߎ ߣߦࠃࠅᡷༀߒ, 㘩㙄៨㘩㊂߽ᷫዋߔࠆ 31)32) ޕ ⣼, ෆᎽ ⢩ 47) 44) 51 , ᔃ⤳, ⢖ 45) , ✂⤑ 46) , ߅ࠃ߮∉⚦ ߥߤߩᧃ᪳⚵❱߿ᄙߊߩ⚦⢩ߢวᚑߐࠇߡ ߎ ࠇ ࠄ ߩ ⚿ ᨐ ߆ ࠄ , BDNF ߪ ៨ 㘩 ᛥ , ߐ ࠄ ߦ ߪ ߅ ࠅ , ⴊ ዊ ᧼ ౝ ߩ BDNF ߪ ߅ ߘ ࠄ ߊ ߎ ࠇ ࠄ ᄙ ߊ ߩ ㊀ࠦࡦ࠻ࡠ࡞ߦ߽㊀ⷐߥ߈ࠍߒߡࠆߣ ⚦ ⢩ ⚵ ❱ ߦ ↱ ᧪ ߔ ࠆ ߢ ࠈ ߁ ߚ ߹ ޕ, BDNF ߪ ⠨߃ࠄࠇࠆޕ ⴊ ᶧ ⣖ 㑐 㐷 (blood brain barrier)ࠍ ㅢ ㆊ ߔ ࠆ 48) ߣ ߁ ႎ ๔ ߽ ࠅ , ⣖ ߽ ⴊ ਛ BDNF ߩ ↱ ᧪ ߩ ৻ ߟ ߣ ⠨ ߃ࠄࠇࠆޕ 3㧕 ࠛ ࡀ ࡞ ࠡ ઍ ⻢ 33) ᧃ ᪳ ᓴ Ⅳ ⴊ ᶧ ਛ ߩ BDNF ߩ ↢ ℂ ⊛ ᓎ ഀ ߿ ᗧ ⟵ ߦ ߦ߽ሽߒ, ߅ߘࠄߊߎߩࠃ߁ߥㇱ 㑐ߒߡߪᧂߛਇߥὐ߽ዋߥߊߥ߇, ⴊዊ᧼ߦ ߩ BDNF ߪ ♧ ઍ ⻢ ߩ ᓮ ߦ ਥ ߣ ߒ ߡ 㑐 ࠊ ߞ ߡ ࠆ ߘߩᄙߊ߇⫾߃ࠄࠇߡࠆߣ߁ߎߣ߆ࠄ, ߚߛ ߣ⠨߃ࠄࠇࠆ ޕታ, ⢈ḩ♧ዩ∛ࡑ࠙ࠬߩ⣖ቶౝ න ߦ ⚵ ❱ ߆ ࠄ ߐ ࠇ ߚ BDNF ߇ ⴊ ᶧ ਛ ߦ ሽ ߒ ࠆ ߪ ⊹ ਅ ߦ BDNF ࠍ ᛩ ਈ ߔ ࠆ ߣ ⴊ ♧ ߇ ૐ ਅ ߔ ߡࠆߩߢߪߥߊ, ࠄ߆ߩᓎഀࠍߪߚߒߡࠆ BDNF ߅ ࠃ ߮ ߘ ߩ ฃ ኈ ߢ ࠆ TrkB ߪ ⤟ ⤳ ߿⣢ ࠆ 15)16) 34) ޕBDNF ߩ ⴊ ♧ 㒠 ਅ ↪ ߩ ⢛ ᥊ ߣ ߒ ߡ , ࡞ࠞࠧࡦỚᐲߩૐਅ ߣ⠨߃ࠄࠇࠆⴊޕዊ᧼ߪ, ฦ⚵❱, ⚦⢩ࡌ࡞ߢ , ࠣ ߩ ᄖ ் ㇱ (traumatic injury)ߢ TrkB ฃ ኈ ࠍ ߔ ࠍᒁ߈ߎߔߎߣ߇⍮ࠄ ࠆ ᧃ ᪳ ⚻ ߿ ઁ ߩ ⚵ ❱ ߩ ୃ ᓳ ࠍ ଦ ߔ ߚ ߦ BDNF BDNF ߪ ⤟ ⤳ ߩ ࠗ ࡦ ࠬ ࡦ Ớ ᐲ ߩ Ⴧ ട 35) 15)35) 41) , ߅ߘࠄ ࠇ ߡ ࠆ ߚ ߹ ޕ, BDNF ᛩ ਈ ߦ ࠃ ࠅ ᮮ 㓒 ⤑ , ᔃ ⤳ , ࠍߔࠆน⢻ᕈ߇ᜰ៰ߐࠇߡ߅ࠅ 㛽ᩰ╭, ⶊ⦡⢽⢌⚦⢩, ⢄⤳ߢߩ♧ขࠅㄟࠍଦㅴ ߊⴊዊ᧼ߦ⫾Ⓧߔࠆߎߣߦࠃߞߡ, ↢ߩ✕ᕆᤨ ߔ ࠆ ߎ ߣ ߦ ࠃ ࠅ , BDNF ߪ ᧃ ᪳ ⚵ ❱ ߢ ߩ ♧ ↪ ࠍ ߦ߃ߡࠆ߽ߩߣផቯߐࠇࠆޕ ⴊ ᶧ ਛ ߩ BDNF ᳓ Ḱ ߪ , ߁ ߟ ∛ ߿ ⍮ ᯏ ⢻ 㓚 ኂ , 㜞ࠆߎߣࠍߒߡ♧ઍ⻢ᡷༀߦ㑐ਈߔࠆߣ⠨ ߃ࠄࠇࠆ 36) ޕ ♧ઍ⻢⇣Ᏹߥߤ᭽∛ߥޘᘒߣⶄ㔀ߦ㑐ㅪߒߡ BDNF ߪ ࠛ ࡀ ࡞ ࠡ ᶖ ⾌ ᯏ ᭴ ߦ ߽ 㑐 ਈ ߒ ߡ ࠆ ޕ ⢈ ḩ ♧ ዩ ∛ ࡑ ࠙ ࠬ ߩ ⣖ ቶ ౝ ࠆ ߪ ⊹ ਅ ߦ BDNF ࠍᛩਈߔࠆߣࠛࡀ࡞ࠡᶖ⾌߇ㅴߔࠆ 15)37)38) ޕ ߐ ࠄ ߦ , BDNF ߪ ࡁ ࡞ ࠛ ࡇ ࡀ ࡈ ࡦ ߩ ઍ ⻢ ࿁ ォ ࠍ ࠆ ∛ ߟ ߁ޕᖚ ⠪ ߢ ߪ ⴊ ᷡ BDNF ᳓ Ḱ ߩ 㗼 ⪺ ߥ ૐ ਅ ࠍ␜ߔߣߩႎ๔ߦട߃ 49)50)51) , ⴊ ᷡ BDNF ߩ ᳓ Ḱ ߪ߁ߟ∝⁁ߩ⹏ଔߣ⽶ߩ⋧㑐㑐ଥ߇ࠆߎߣ߽ ႎ๔ߐࠇߡࠆ 49)51) ޕ ㅴ ߐ ߖ , ⶊ ⦡ ⢽ ⢌ ⚵ ❱ ߩ uncoupling protein-1 ࠕ ࡞ ࠷ ࡂ ࠗ ࡑ ∛ ᖚ ⠪ ߦ ߅ ߡ ߽ ⴊ ᷡ BDNF ߪ mRNA (UCP1) ⊒ ࠍ 㜞 ࠆ ߎ ߣ ߽ ႎ ๔ ߐ ࠇ ߡ ૐਅߒߡ߅ࠅ, ⍮ᯏ⢻ߩ⹏ଔߣߒߡᐢߊ⥃ᐥ⊛ 39) BDNF ߪ ਛ ᨔ ⚻ ♽ ߦ ↪ ࠄ ࠇ ߡ ࠆ Mini-Mental State Examination ࠍߒߡᗵ⚻♽ࠍᵴᕈൻߒ, ⢈ḩ♧ዩ∛ࡑ࠙ (MMSE) scores ߣ ᱜ ߩ ⋧ 㑐 㑐 ଥ ߇ ࠄ ࠇ ߡ ࠬߩࠛࡀ࡞ࠡᶖ⾌㊂ࠍᓮߒߡࠆ߽ߩߣ⠨ ࠆ ߃ࠄࠇࠆޕ ⠪ 35 ฬ ࠍ ኻ ⽎ ߣ ߒ ߚ ⎇ ⓥ ߦ ߅ ߡ ߽ MMSE ߣ ᱜ ࠆ ߩࠄࠇߎޕᚑ❣߆ࠄ, 52) ߚ ߹ޕ, ⴊ ᷡ BDNF ߪ ⍮ ∝ ߩ ߥ ஜ Ᏹ 㜞 㦂 ߩ⋧㑐㑐ଥ߇ࠆߎߣ 4. ⴊ ਛ ߩ $&0( , 57㨪 79 ᱦ ߩ ↵ ᅚ 1398 ฬࠍኻ⽎ߣߒߚᄢⷙᮨ∉ቇ⺞ᩏߢ߽, ᅚᕈߢߪⴊ BDNF ߪ ਛ ᨔ ⚻ ♽ ߦ ᄙ ߊ ሽ ߒ ߡ ࠆ ߇ , ⴊ ᶧਛߦ߽ሽߔࠆ 53) 40) ⴊޕਛ BDNF ߦ ߪ , ⴊ ዊ ᧼ ౝ ẏ BDNF ᳓ Ḱ ߩ ૐ ୯ ߪ ⍮ ᯏ ⢻ ߩ ૐ ਅ ߣ 㑐 ㅪ ߔ ࠆ ߎߣ߇ႎ๔ߐࠇߡࠆ ߦࠬ࠻࠶ࠢߐࠇߡࠆ߽ߩߣⴊẏਛߦࡈߩ 54) ޕ ㄭᐕ, ࠕ࡞࠷ࡂࠗࡑ∛߿߁ߟ∛ߣ♧ઍ⻢⇣Ᏹ 55) ߪᧂᴦ ⁁ ᘒ ߢ ሽ ߔ ࠆ ߽ ߩ ߩ 2 ⒳ 㘃 ߇ ࠅ , ⴊ ᷡ BDNF ߣߩ㑐ㅪ߇ᜰ៰ߐࠇߡࠆ߇, ╩⠪ࠄ ߪ ਔ ⠪ ࠍ , ⴊ ẏ BDNF ߪ ᓟ ⠪ ߩ ߺ ࠍ ␜ ߒ ߡ ࠆ ߣ ≮ᧂߢᲧセ⊛⊒∝ᣧᦼߣ⠨߃ࠄࠇࠆ 2 ဳ♧ዩ ⠨߃ࠄࠇߡࠆⴊޕዊ᧼ౝߦ⫾߃ࠄࠇߡࠆ ∛ ᖚ ⠪ ߢ ߪ ⴊ ᷡ BDNF ߩ Ⴧ ട ߦ ട ߃ , ⴊ ♧ ୯ ߿ ਛ BDNF ߪ , ⴊ ዊ ᧼ ߩ ᵴ ᕈ ൻ ߿ ಝ ࿕ ߩ ㆊ ⒟ ߢ ߐ ᕈ ⢽ ⢌ , LDL ࠦ ࠬ ࠹ ࡠ ࡞ ߥ ߤ ߩ ♧ ⢽ ⾰ ઍ ⻢ 40)41) ⴊޕዊ ᧼ ౝ ߦ ߪ ⴊ ਛ ߩ 90㧑 એ ߩ BDNF ᜰᮡߣߩ㑆ߦᱜߩ⋧㑐㑐ଥ߇ࠆߎߣࠍႎ๔ߒ ߇ ⫾ ߃ ࠄ ࠇ ߡ ࠆ ߇ , ⴊ ዊ ᧼ ߢ ߩ mRNA ⊒ ࡌ ߚ ৻ ޕᣇ , 2 ဳ ♧ ዩ ᖚ ⠪ ߩ ⴊ ᷡ ߮ ⴊ ẏ BDNF ᳓ ࡞ ߪ ૐ ୯ ߢ ࠆ ߎ ߣ ߆ ࠄ , ઁ ߩ ⚵ ❱ ߆ ࠄ BDNF ࠍ Ḱ ᓧ ߡ ࠆ ߣ ⠨ ߃ ࠄ ࠇ ࠆ ޕBDNF ߪ 㛽 ᩰ ╭ ߿ ᧃ ᪳ ߩਇ৻⥌ߪ, ߅ߘࠄߊኻ⽎⠪ߩⴊ▤ว૬∝ࠍ ࠇࠆ ⚻, ⤟⤳, ⴊ▤ౝ⊹⚦⢩, ᄢേ⣂ 43) , ⣢⤳, 㗶ਅ 56) ߪ ૐ ਅ ߒ ߡ ࠆ ߣ ߩ ႎ ๔ ߽ ࠆ ࠄ ࠇ ߎޕᚑ ❣ ߚ∛ᦼࠬ࠹ࠫߩ⋧㆑߇ᓇ㗀ߒߡ߅ࠅ, ⠴♧⢻㓚 ஜ ᐽ ⑼ ቇ ╙ 31 Ꮞ 52 ኂ ߩ ⊒ ∝ ೋ ᦼ ߦ ߪ ઍ ఘ ⊛ ߦ BDNF ߇ Ⴧ ട ߒ , ࠗ ࡦ ࡔ ╭ ߦ ߅ ߌ ࠆ BDNFmRNA, ࠲ ࡦ ࡄ ࠢ ⾰ ⊒ ߪ ࠬࡦ↪ਇ⿷ࠍߚ∛ᘒߩㅴⴕߦⴊਛ ㆇേ 2 ᤨ㑆ᓟߦჇടߔࠆߎߣ߇⏕ߐࠇߡࠆ BDNF ߪ ૐ ਅ ߒ ߡ ߊ น ⢻ ᕈ ߽ ⠨ ߃ ࠄ ࠇ ࠆ ޕ 57)58) ৻ޕᣇ , ᶏ 㚍 㗔 ၞ ߩ BDNFmRNA 1 3 ) 6 2 ) ⊒ ߪ 㜞 ߹ࠆߣߔࠆႎ๔߇ᄙ߽ߩߩ, ࠲ࡦࡄࠢ⾰⊒ߦ ⴊ ਛ BDNF ᳓ Ḱ ߩ ૐ ਅ ߇ ⚵ ❱ ߦ ߅ ߌ ࠆ BDNF ว 61) ࠆ ߆ ߆ޕᚑ ❣ ᚑ㊂ߩᷫዋߦࠃࠆ߽ߩߥߩ߆, ⚵❱߳ߩขࠅㄟߺ 㑐ߒߡߪᔅߕߒ߽৻⥌ߒߡߥ ㅴߩ⚿ᨐࠍᤋߒߚ߽ߩߢࠆ߆ߪਇߢ ߩ ਇ ৻ ⥌ ߩ ⷐ ࿃ ߣ ߒ ߡ , ⣖ ౝ ߪ BDNFmRNA ߩ ಽ ࠆ ߇ , ⴊ ਛ ߩ BDNF ߇ ∛ ᘒ ߩ ⊒ ∝ ㅴ ዷ ߩ ㆊ ⒟ ߢ ⸃ㅦᐲ߇ㅦߚ, ᶏ㚍ߩ៰ᛛⴚ߿᷹ቯᗵᐲߥ ࠄ߆ߩᓎഀࠍᨐߚߒߡࠆߣ⠨߃ࠄࠇߡࠆޕ ߤߩ᷹ቯᛛⴚߩᏅ㆑߿, ᢿ㗡ߩ࠲ࠗࡒࡦࠣߥߤ߇ ᓇ㗀ߒߡࠆน⢻ᕈ߇ࠆޕ 5. ㆇ േ ߣ ⚵ ❱ ߩ $&0( 9 ) 1 0 ) 11 ) ⴊ ਛ BDNF ߩ ߺ ߥ ࠄ ߕ , ߁ ߟ ∛ ᖚ ⠪ 12) ߿㊀ 3㧕 㐳 ᦼ ࠻ ࠾ ࡦ ࠣ ߩ ᓇ 㗀 ߢ ߪ ᶏ 㚍 ߩ BDNF ⊒ 2 ㅳ㑆એߩ㐳ᦼߩ࠻࠾ࡦࠣߢߪ, ᶏ㚍ߦ ૐਅ߽ႎ๔ߐࠇߡࠆߦ߁ࠃߩߎޕ, ߁ߟ߿ࠕ ߅ ߌ ࠆ BDNF ߩ ࠲ ࡦ ࡄ ࠢ ⾰ ߅ ࠃ ߮ mRNA ߣ ߽ ߦ ⊒ ᐲࠕ࡞࠷ࡂࠗࡑ∛ᖚ⠪ ࡞ ࠷ ࡂ ࠗ ࡑ ∛ ߦ ߪ BDNF ߩ ᷫ ዋ ߇ ߘ ߩ ∛ ᘒ ᚑ ┙ ߇Ⴧടߔࠆߎߣߢ, ᚑ❣ߩ৻⥌ࠍߺߡࠆ ߿ ⊒ ∝ㅴ ዷ ߦ ࠄ ߆ ߩ ᓎ ഀ ࠍ ᨐ ߚ ߒ ߡ ࠆ ߎ ߣ 60)61) ޕ ߇ផቯߐࠇࠆ߇, ৻ᣇㆇേߪᶏ㚍ࠍߪߓߣߔࠆ 13)14) 57)58) ߢߩ એߩࠃ߁ߦ, ⚵❱ߦࠃߞߡᄙዋߩᤨ㑆Ꮕߪ ߩ⊒ࠍ㜞ࠆߎߣ߇ᄙ ࠆ ߽ ߩ ߩ , ⍴ ᦼ ߅ ࠃ ߮ 㐳 ᦼ ߩ ㆇ േ ߦ ࠃ ࠅ BDNF ⊒ ߊ ߩ േ ‛ ታ 㛎 ߢ ⏕ ߐ ࠇ ߡ ࠆ ޕએ ਅ ߦ ᕆ ᕈ ㆇ േ , ߪ Ⴧ ട ߔ ࠆ ߣ ⠨ ߃ ࠄ ࠇ ࠆ ޕ⣄ 㜑 ߿ ࡅ ࡔ ╭ ߦ ߅ ⍴ᦼ߅ࠃ߮㐳ᦼ࠻࠾ࡦࠣߩᓇ㗀ߦߟߡ, ߎ ߌ ࠆ BDNF ⊒ ߩ Ⴧ ട ߇ ↢ ߦ ߆ ߥ ࠆ ല ᨐ ࠍ ߽ ࠇ߹ߢߩേ‛ታ㛎ߦ߅ߌࠆᚑ❣ࠍⷐ⚂ߔࠆޕ ߚ ࠄ ߔ ߆ ߪ ਇ ߢ ࠆ ߒ ߆ ߒ ޕ, TrkB ᛫ ᛩ ਈ ߦ ⣖ౝߩ᭽ߥޘ㗔ၞ BDNF ߿ TrKB ฃ ኈ 59) ߦട߃㛽ᩰ╭ ࠃ ࠅ ⣖ BDNF ߩ TrkB ߳ ߩ ⚿ ว ࠍ 㒖 ኂ ߔ ࠆ ߣ , ㆇ 1㧕 ᕆ ᕈ ㆇ േ ߩ ᓇ 㗀 1995 ᐕ ߦ Nepper ࠄ േߦ߁ቇ⠌⸥ᙘ⢻ജߩะߪࠄࠇߕ, ߐࠄ 13) ߇ ㆇ േ ߦ ࠃ ߞ ߡ ߦ BDNF ࡋ ࠹ ࡠ ࡁ ࠶ ࠢ ࠕ ࠙ ࠻ ࡑ ࠙ ࠬ ߢ ߪ ㆇ േ ᓟ ߩ 63) BDNFmRNA ߇ Ⴧ ട ߔ ࠆ ߣ ߁ ߎ ߣ ࠍ ೋ ߡ ႎ ๔ ᛫߁ߟലᨐߪߺࠄࠇߥ߆ߞߚߎߣߥߤࠃࠅ ߒ ߡ એ ᧪ , ㆇ േ ߇ BDNF ߦ ߷ ߔ ᓇ 㗀 ߦ ߟ ߡ ߪ ዋ ߥ ߊ ߣ ߽ ⣖ ౝ ߩ BDNF㧙 TrkB ࠪ ࠣ ࠽ ࡞ વ ㆐ ♽ ᢙ ᄙ ߊ ߩ ⎇ ⓥ ߇ ߥ ߐ ࠇ ߡ ߈ ߚ ޕᓐ ࠄ 13) ߪ, 㧝࿁ߩ , ߩㅴߪㆇേߩ߽ߚࠄߔ⣖ᯏ⢻߳ߩࡊࠬലᨐ ⥄ ⊒ ㆇ േ ߦ ࠃ ࠅ ᶏ 㚍 ߩ mRNA ⊒ ߇ Ⴧ ട ߔ ࠆ ߎ ࠍખߒߡࠆߩߢࠈ߁ޕ ߣࠍႎ๔ߒߡࠆޕห᭽ߩ⚿ᨐߪ, ࠻࠶࠼ࡒ࡞ 6.ⴊ ਛ $&0( ߦ ኻ ߔ ࠆ ㆇ േ ߩ ᓇ 㗀 ࠍ ↪ ߚ ᒝ ㆇ േ ߦ ࠃ ߞ ߡ ߽ ࠄ ࠇ , Huang ࠄ 60) ߪ∋ഭ࿎ᘻߦ⥋ࠆ㜞ᒝᐲߩㆇേ 2 ᤨ㑆ᓟߦ േ‛ታ㛎ߩ⚿ᨐ߆ࠄ, ㆇേߦࠃࠅ⣖߿㛽ᩰ╭ߢ BDNFmRNA, ࠲ ࡦ ࡄ ࠢ ⾰ ߣ ߽ ߦ Ⴧ ട ߔ ࠆ ߎ ߣ ࠍ ߩ BDNF ⊒ ߇ 㜞 ߹ ࠆ ߎ ߣ ߪ , ৻ ⽾ ߒ ߡ ⏕ ߐ ࠇ ႎ ๔ ߒ ߡ ࠆ ߒ ߆ ߒ ޕ, BDNF ࠲ ࡦ ࡄ ࠢ ⾰ ߪ 1 ࿁ ߡ ࠆ ߇ , ⴊ ਛ ߩ BDNF ߪ ᕆ ᕈ ࠆ ߪ ᘟ ᕈ ߩ ㆇ ߩㆇേߢߪჇടߒߥߣߩႎ๔߽ࠅ 61) , ࠲ࡦ േ ߦ ኻ ߒ ߡ ߆ ߥ ࠆ ᔕ ╵ ࠍ ␜ ߔ ߩ ߢ ࠈ ߁ ߆ ޕએ ࡄࠢ⾰⊒ߦ㑐ߔࠆᕆᕈㆇേߩ⚿ᨐߪ৻⥌ߒߡ ਅ, ߘߩὐߦߟߡⷐ⚂ߔࠆޕ ߥ ޕᕆ ᕈ ㆇ േ ᓟ ߩ BDNF ⊒ ߦ 㑐 ߔ ࠆ ࠲ ࠗ ࡓ ࠦ ࠬ ߇ ㇱ ߦ ᬌ ⸛ ߐ ࠇ ߡ ࠆ ޕ⣄ 㜑 ߦ ߅ ߌ ࠆ 1㧕 ᣣ Ᏹ ⊛ ߥ ㆇ േ ⠌ ᘠ ߩ ᓇ 㗀 BDNFmRNA ⊒ ߪ , ㆇ േ ⚳ ੌ ᓟ 6 ᤨ 㑆 ᓟ ߹ ߢ ߪ ╩ ⠪ ࠄ 64)ߪ , ᣣ Ᏹ ⊛ ߥ ㆇ േ ⠌ ᘠ ߇ 㕒 ᤨ ߩ ⴊ ᷡ 57) , ࡅࡔ╭ߢߪ ߮ ⴊ ẏ BDNF ᳓ Ḱ ߦ ߆ ߥ ࠆ ᓇ 㗀 ࠍ ߷ ߔ ߩ ߆ BDNFmRNA ⊒ ߪ 12 ᤨ 㑆 ᓟ ߦ , ࠲ ࡦ ࡄ ࠢ ⾰ ⊒ ࠍ ᬌ ⸛ ߒ ߚ ޕ20 ᱦ ઍ ߩ ஜ Ᏹ ↵ ሶ ᄢ ቇ ↢ ࠍ ኻ ⽎ ߦ , ᄌൻ߇ࠄࠇߡ߅ࠄߕ ߪ 24 ᤨ 㑆 ᓟ ߦ Ⴧ ട ߔ ࠆ ߎ ߣ ߇ ⏕ ߐ ࠇ ߡ ࠆ 58) ޕ ┹ᛛߣߒߡᣣᏱ⊛ߦᲧセ⊛ᒝᐲߩ㜞ㆇേࠍⴕ ߞ ߡ ࠆ ⠪ (┹ ᛛ ⠪ 㧦 n=12)ߣ ో ߊ ㆇ േ ⠌ ᘠ ߇ ߥ 2㧕 ⍴ ᦼ ࠻ ࠾ ࡦ ࠣ ߩ ᓇ 㗀 1 ㅳ㑆એਅߩ࠻࠾ࡦࠣߢߪ, ⣄㜑߅ࠃ߮ࡅ ߽ ߩ (㕖 ㆇ േ ⠪ 㧦 n=14)ࠍ Ყ セ ᬌ ⸛ ߒ ߚ ⚿ ߩ ߘޕᨐ , ┹ ᛛ ⠪ ߩ ⴊ ᷡ BDNF ᳓ Ḱ ߪ ᗧ ߦ ૐ ߊ , ߐ ࠄ ߦ ട ⣖↱᧪⚻ᩕ㙃࿃ሶ㧔BDNF㧕ߩᓎഀߣㆇേߩᓇ㗀 53 ㅦ ᐲ ⸘ ߢ ᷹ ቯ ߒ ߚ り ᵴ േ ㊂㧔 ✚ ࠛ ࡀ ࡞ ࠡ ᶖ ⾌ BDNF ߩ Ⴧ ട ߦ ߟ ߥ ߇ ࠅ , ߘ ࠇ ߇ ㆇ േ ߦ ࠃ ࠆ ⍮ ㊂, ㆇേߦࠃࠆࠛࡀ࡞ࠡᶖ⾌㊂, ᱠᢙ㧕ߣߩ㑆 ᯏ⢻߿߁ߟ, ⒳ߩޘઍ⻢ᡷༀߦነਈߒߡࠆߣ߽ ߦ ⽶ ߩ ⋧ 㑐 㑐 ଥ ߇ ࠄ ࠇ ߚ ৻ ޕᣇ , ⴊ ẏ BDNF ⠨ ߃ ࠄ ࠇ ࠆ ޕㆇ േ ᓟ ᢙ ᤨ 㑆 ᓟ ߦ ࠄ ࠇ ߚ BDNF ᳓ ߪਔ⟲ߢᗧᏅߪߥߊ, ⸥ߩࠃ߁ߥ㑐ㅪᕈ߽ Ḱߩૐਅߪ, ߅ߘࠄߊ⚵❱ߢߩ↪߇㜞߹ߞߚߎ ߥ߆ߞߚޕㆇേߩ⹏ଔᴺߪ⇣ߥࠆ߽ߩߩ, 㘃ૃ ߣࠍᤋߒߡࠆߩߢࠈ߁ޕᓟ, ᕆᕈㆇേߦ ߩ ᚑ ❣ ߪ Chan ࠄ 65) ߦࠃߞߡ߽ႎ๔ߐࠇߡࠆޕ ᓐ ࠄ ߪ 20~50 ᱦ ઍ ߩ ஜ Ᏹ ߥ ↵ ᅚ 85 ฬ ࠍ ኻ ⽎ ߦ , ⾰ ࠃ ࠆ ⴊ ᷡ BDNF േ ᘒ ߦ 㑐 ߔ ࠆ ᯏ ᐨ ߩ ⸃ ߇ ᦼ ᓙ ߐ ࠇࠆޕ ⚕ ߢ ᓧ ࠄ ࠇ ߚ り ᵴ േ ㊂ ߣ ⴊ ᷡ BDNF ᳓ Ḱ ߣ ߩ 㑆ߦ⽶ߩ⋧㑐㑐ଥࠍߡࠆޕ 3㧕 㐳 ᦼ ߩ ㆇ േ ߩ ᓇ 㗀 ┹ ᛛ ⠪ ߢ ࠄ ࠇ ߚ ⴊ ᷡ BDNF ߩ ૐ ਅ ߪ , ㆇ േ ߎ ࠇ ߹ ߢ ߦ , 㐳 ᦼ ߩ ㆇ േ ߇ ⴊ ᶧ ਛ ߩ BDNF ߩ ᳓ ⛮⛯ߦࠃࠆ㛽ᩰ╭߿⚻៊்ߩୃᓳㆊ⒟ߦ߅ߌ Ḱߦ߷ߔᓇ㗀ࠍᬌ⸛ߒߚ⎇ⓥߪ, ╩⠪ࠄ߇⍮ࠅ ࠆઍఘ↪ߣߒߡߩ⚵❱ขࠅㄟߺߩჇᄢࠍᤋ ᓧ ߚ ▸ ࿐ ߢ 3 ႎ ๔ ࠆ ޕLevinger ࠄ ߒߡࠆߩ߆߽ߒࠇߥ৻ޕᣇ, ៨㘩ᛥ߿♧ઍ ߥ ㆇ േ ⠌ ᘠ ࠍ ߐ ߥ ஜ Ᏹ ߥ ਛ 㜞 ᐕ 49 ੱ㧔 50.9 ± ⻢, ࠛࡀ࡞ࠡઍ⻢ㅴࠍଦߔᔅⷐ߇ዋߥߚ 6.2 ᱦ 㧕 ࠍ ኻ ⽎ ߦ 8 ⒳ ⋡ ߩ ㆇ േ ߢ ᭴ ᚑ ߐ ࠇ ߚ ࠫ ߦ , ㆇ േ ߦ ࠃ ࠆ ㆡ ᔕ ⽎ ߣ ߒ ߡ ⚵ ❱ ߢ ߩ BDNF ว ࠬ ࠲ ࡦ ࠬ ㆇ േ ࠍ ㅳ 3 ࿁ , 10 ㅳ 㑆 ⴕ , ೨ ᓟ ߢ ᚑ ㊂ ߇ ᛥ ߐ ࠇ , ߘ ߩ ⚿ ᨐ ߣ ߒ ߡ ⴊ ᷡ BDNF ᳓ Ḱ ⴊ ẏ BDNF ᳓ Ḱ ࠍ Ყ セ ߒ ߚ ╙ ࠣ ࡦ ࠾ ࠻ޕ1 ㅳ ߇ૐ୯ߢߞߚߣ߽⠨߃ࠄࠇࠆࠃߖߦࠇߕޕ, ߪ 㧝 RM(repetition maximum)ߩ 40㨪 50㧑 ⋧ ᒰ ࠍ 15 ߎࠇࠄߪోߡᮮᢿ⎇ⓥߢࠅߘߩ࿃ᨐ㑐ଥߪਇ 㨪 20 ᓳ ࠍ 2 ࠶ ࠻ ⴕ , 2 ㅳ ⋡ એ 㒠 ߪ 㧝 RM ߩ ߩ ߹ ߹ ߢ ࠆ ޕBDNF ࡋ ࠹ ࡠ ࡁ ࠶ ࠢ ࠕ ࠙ ࠻ ࡑ ࠙ 50㨪 85㧑 ߢ 8㨪 20 ᓳ ࠍ 3 ࠶ ࠻ ⴕ ߞ ߚ ⚿ ߩ ߘޕ ࠬߣ㊁↢ဳࡑ࠙ࠬߩᵴേ㊂ࠍᲧセߔࠆߣ೨⠪ߩ ᨐ, ࠻࠾ࡦࠣᓟߦ╭ജ߿㒰⢽⢌㊂ߪჇടߒߚ 66) 73) ߪ, ᣣᏱ⊛ , ᣣ ߽ ߩ ߩ , ⴊ ẏ BDNF ᳓ Ḱ ߪ ᄌ ൻ ߖ ߕ , ࡔ ࠲ ࡏ ࠶ Ᏹ ⊛ ߥ ㆇ േ ⠌ ᘠ ߇ ⴊ ᷡ BDNF ࠍ ૐ ਅ ߐ ߖ ࠆ ߆ ࠍ ࡅ ࠢࠪࡦ࠼ࡠࡓߩ᭴ᚑ࿃ሶᢙߦ߽ᓇ㗀ࠍࠄ ࠻ߦ߅ߡ⚿⺰ߔࠆߦߪ㐳ᦼ⎇ⓥ߇ᔅⷐߣ ࠇ ߥ ߆ ߞ ߚ ޕSchiffer ࠄ ⠨߃ࠄࠇࠆޕ 27 ੱ ࠍ ኻ ⽎ ߦ 12 ㅳ 㑆 ߩ ࠫ ࠬ ࠲ ࡦ ࠬ ㆇ േ ߦ ࠃ ࠆ ߶߁߇㜞୯ߢࠆߎߣ߇⏕ߐࠇߡ߅ࠅ 74) ߽ห᭽ߦஜᏱߥᄢቇ↢ ࠍ ⴕ ߞ ߚ ߇ , ⴊ ẏ BDNF ߩ ᳓ Ḱ ߪ ᄌ ൻ ࠍ ߕ, ߐࠄߦਛ╬ᐲߩᜬਭ⊛ㆇേߦࠃߞߡ߽ⴊẏ 2㧕 ᕆ ᕈ ߩ ㆇ േ ߩ ᓇ 㗀 ߎ ࠇ ߹ ߢ , ᕆ ᕈ ߩ ㆇ േ ߇ ⴊ ਛ BDNF ᳓ Ḱ ߦ ߷ ߔᓇ㗀ߦߟߡߪ, ߊߟ߆ߩᚑᨐ߇ႎ๔ߐࠇߡ ࠆ㧔 1㧕ޕਛ ╬ ᐲ એ ߩ ᒝ ᐲ ߦ ࠃ ࠆ ᕆ ᕈ ㆇ േ ߢ BDNF ߦ ᗧ ߥ ᄌ ൻ ߇ ࠄ ࠇ ߥ ߆ ߞ ߚ ߎ ߣ ࠍ ႎ ๔ߒߡࠆޕ ৻ ᣇ , Castellano ࠄ 72) ߪ, ᄙ⊒ᕈ⎬ൻ∝ᖚ⠪ ߪ , ⴊ ᷡ BDNF ߪ ৻ ᤨ ⊛ ߦ Ⴧ ട ߒ , ㆇ േ ਛ ᱛ ᓟ ⋥ (n = 11㧧 ↵ ᕈ 3㧘 ᅚ ᕈ 8, 40±10 ᱦ ) ߣ ᕈ , ᐕ 㦂 ࠍ ߜ ߦ 㕒 ᤨ ᳓ Ḱ ߹ ߢ ᚯ ࠆ ߎ ߣ ߢ ৻ ⥌ ߒ ߡ ࠆ ߎޕ ࡑ ࠶ ࠴ ࡦ ࠣ ߒ ߚ ஜ Ᏹ ⠪ (n = 11) ࠍ ኻ ⽎ ߦ VO 2 p e a k ࠇ ߹ ߢ ߦ , BDNF ߩ Ⴧ ട ߳ ߩ ㆇ േ ᒝ ᐲ ߩ ଐ ሽ ᕈ ߦ ߩ 60㧑 ߩ ᒝ ᐲ ߢ 30 ಽ 㑆 ߩ ⥄ ォ ゞ ㆇ േ ࠍ ㅳ 3 ࿁ , 8 ߟߡߪஜᏱ⠪ࠍኻ⽎ߦᬌ⸛ߒߚ⎇ⓥ߇ 2 ႎ๔ ㅳ㑆ߩ࠻࠾ࡦࠣࠍⴕ, 㐿ᆎ೨ߣ 4 ㅳ㑆 ࠆ ߇ , ߕ ࠇ ߽ ૐ ᒝ ᐲ ߢ ߪ ⴊ ᷡ BDNF ߪ Ⴧ ട ߒ ߥ ᓟ߅ࠃ߮ 8 ㅳ㑆ᓟߦណⴊࠍⴕߞߚ⚿ߩߘޕᨐ, ᄙ 68)69) ߚ ߹ޕ, ㆇ േ ᓟ ߩ ⴊ ⊒ ᕈ ⎬ ൻ ∝ ᖚ ⠪ ߢ ߪ ⴊ ᷡ BDNF ᳓ Ḱ ߪ 4 ㅳ ⋡ ߦ ᷡ BDNF ߩ േ ᘒ ߦ 㑐 ߒ ߡ ߪ , ᦨ 㐳 ߢ ㆇ േ ਛ ᱛ ᓟ 3 Ⴧ ട , 8 ㅳ ⋡ ߢ ߪ ࡌ ࠬ ࠗ ࡦ ߩ ᳓ Ḱ ߦ ᚯ ߞ ߚ ৻ޕ ᤨ㑆߹ߢ⏕ߐࠇ, ਛᱛᓟ⋥ߜߦ㕒ᤨ᳓Ḱ߹ߢ ᣇ , ஜ Ᏹ ⠪ ߢ ߪ ⴊ ᷡ BDNF ߩ ᳓ Ḱ ߦ ᗧ ߥ ᄌ ൻ ߪ ࿁ ᓳ ߒ , 2㨪 3 ᤨ 㑆 ᓟ ߢ ߪ 㕒 ᤨ ᳓ Ḱ ࠃ ࠅ ߽ ߐ ࠄ ߦ ࠄࠇߥ߆ߞߚߣႎ๔ߒߡࠆޕ ߎߣ߇ႎ๔ߐࠇߡࠆ ૐਅߔࠆߣߩႎ๔߽ࠆ 72) ޕ એ ߩ ߏ ߣ ߊ , ஜ Ᏹ ⠪ ߢ ߪ ⴊ ਛ BDNF ᳓ Ḱ ߪ ዋ ᕆ ᕈ ㆇ േ ߦ ࠃ ࠆ ⴊ ਛ BDNF ᳓ Ḱ ߩ ৻ ㆊ ᕈ ߇ ߥ ߊ ߣ ߽ 2㧘3 ࠞ ߩ ਛ , ⍴ ᦼ ⊛ ߥ ࠻ ࠾ ࡦ ࠣ ߢ ߆ߥࠆ⚵❱߆ࠄߩߢࠅ, ߘߩჇട߇ߤߩ ߪ ᄌ ൻ ߒ ߥ ߎ ߣ ߢ ৻ ⥌ ߒ ߡ ࠆ ߒ ߆ ߒޕႎ ๔ ᢙ ࠃ߁ߥ↢ℂ↪ࠍߔࠆߩ߆ߪਇߩ߹߹ߢ ߽ዋߥߊ, ㆇേߩ⒳㘃, ᒝᐲߩ⋧㆑ߦട߃, ㆇേ ࠆߒ߆ߒޕ, ᕆᕈㆇേߦࠃߞߡోりࠍᓴⅣߔࠆ ⠌ᘠߩή, ᕈ, ᐕ㦂ߥߤࠍ㒢ቯߒߚኻ⽎⠪ߢߩ BDNF ߇ Ⴧ ട ߔ ࠆ ߎ ߣ ߪ , ⚵ ❱ ߢ ↪ ߢ ߈ ࠆ ᦝߥࠆᬌ⸛߇ᔅⷐߢࠈ߁ޕ 健 康 科 学 54 7. ま と め と 今 後 の 課 題 第 31 巻 も 少 な く な い 。血 中 の BDNF は 約 90%が 血 小 板 内 BDNF の 生 理 学 的 役 割 と 意 義 , お よ び 運 動 に よ に存在するが, 多くは他の組織で産生されたる影 で あ り , 近 年 , ”metabotorophin”と し て の 概 念 も 提 響 に つ い て 概 説 し た 。 BDNF の 生 理 作 用 は 多 彩 唱されている 75) 。 し か し , BDNF の 役 割 に つ い て BDNF が 血 小 板 内 に 取 り 込 ま れ 備 蓄 し て い る と 考 41) 。し か し , た だ 単 に 組 織 か ら 漏 れ 出 た は多くが動物実験に基づいており, ヒトにおける えられる 臨 床 的 研 究 は 極 め て 少 な い の が 現 状 で あ る 。特 に BDNF が 血 中 に 存 在 し て い る の で は な く , 静 脈 投 血 中 BDNF に 関 し て は 様 々 な 疾 病 と の 関 連 が 指 摘 与 に よ っ て BDNF は 血 糖 降 下 作 用 等 の 生 理 活 性 を されているものの, その役割や意義など不明な点 示すことからも 36)37) , 血 中 BDNF は 何 ら か の 生 BDNFの の変 変化 化に に関 関す する る成 成績 の 要 約 表表 １ １ 急急 性性 運運 動動 にに よよ るる 血血清清BDNF 著者（年） 対象者 対象者 著者（年） Gold Gold らら 67) 67) (2003) (2003) 人数と性別 人数と性別 多多 発発 性性 2525 年齢 年齢 運動の形式 運動の形式 強度 強度 時間 時間 血清 BDNF の変化 血清 BDNF の変化 39.2±1.8 39.2±1.8 自転車エル 自転車エル 60%VO max 60%VO22max 3030分分 両群とも運動終了直後に増 両群とも運動終了直後に増 (男9,9,女女16) 16) 硬硬 化化 症症 (男 加。30 分後は安静状態に戻 加。30 分後は安静状態に戻 ゴメーター ゴメーター 患者 患者 健常者 健常者 った。 った。 2020 40.5±2.0 40.5±2.0 (男14, 14,女女4)4) (男 Rojas Rojas らら 競技者 競技者 男(8) 男(8) 24.6±1.3 24.6±1.3 68) 68) (2006) (2006) 自転車エル 自転車エル 22 W·kg W·kg11 の の負 負荷 荷でで 1010分分 ゴメーター ゴメーター 70 70 rpm（ウォーミング rpm（ウォーミング 変化なし。 変化なし。 アップ） アップ） 1 最初の 運動終了 3 3 。 疲疲 労労 終了直後に増加。 最初の22分は 分は22W·kg W·kg 1。 終了直後に増加。 運動終了 その後 その後 30 30 秒毎に 秒毎に25W 25W 困困 憊憊 分後には安静時と同レベル 分後には安静時と同レベル ずつ増加。 （ランプテス ずつ増加。 （ランプテス まで まで に回復。 に回復。 ト） ト） Ferris Ferris らら 健常者 健常者 69) 69) 1616 25.4±1.0 25.4±1.0 (男4,4,女女11) 11) (男 (2007) (2007) エルゴメー エルゴメー ター ター 多段階運動負荷試験 多段階運動負荷試験 運動直後に増加。 運動直後に増加。 換気閾値より 換気閾値より10%高い 10%高い 3030分分 運動直後に増加。 運動直後に増加。 強度（高強度） 強度（高強度） 30% 換気閾値より 換気閾値より20%低い 20%低い 30% 変化なし。 変化なし。 強度（低強度） 強度（低強度） Tang Tang らら 健常者 健常者 70) 70) 1616 19-30 19-30 (男8,8,女女8)8) (男 (2008) (2008) ステップ運 ステップ運 1515分分 動 動 運動直後に増加。25 分後に 運動直後に増加。25 分後に は安静状態と同レベルに回 は安静状態と同レベルに回 復。 復。 Rojas Rojas らら 71) 71) (2008) (2008) 脊髄損傷 男(11) 男(11) 脊髄損傷 40.6±6.3 40.6±6.3 のある競 のある競 ハンドバイ ハンドバイ ウ ウォ ォー ーミ ミン ング グア アッ ッププ 1010分分 ク ク （54%HRmax） （54%HRmax） 技者 技者 42km 42km のタイムトライ のタイムトライ 運動直後に増加。 運動直後に増加。 変化なし。 変化なし。 アル（89%HRmax） アル（89%HRmax） Castellano Castellano 72) 72) ら(2008) ら(2008) 多発性 多発性 1111 硬化症 硬化症 (男3,3,女女8)8) (男 40±10 40±10 ゴメーター ゴメーター 患者 患者 健常者 健常者 1111 (男3,3,女女8)8) (男 自転車エル 自転車エル 40±10 40±10 60%VO2peak 60%VO2peak 3030分分 運動終了 2, 2, 3 時間後では安 運動終了 3 時間後では安 静時のレベルよりも低下。 静時のレベルよりも低下。 ⣖↱᧪⚻ᩕ㙃࿃ሶ㧔BDNF㧕ߩᓎഀߣㆇേߩᓇ㗀 55 ℂ ⊛ ߥ ᓎ ഀ ࠍ ᜂ ߞ ߡ ࠆ ߣ ផ ᷹ ߐ ࠇ ࠆ ߢ ߹ ࠇ ߎޕ, dementia among persons 65 years of age and ࠶ ࠻ ߩ ᄢ ⣖ ⊹ ⾰ BDNF ߣ ⴊ ᷡ BDNF ㊂ ߪ ᚑ 㐳 ߩ older. 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