BIOCHEMISTRY & MOLECULAR BIOLOGY
HIGHER NERVOUS SYSTEM
KAMPO MEDICINE

Dr. HIROYUKI OHYAMA.（Ph.D）

　　

Age-related difference in synaptosomal membrane fluidity
Biochemistry and Molecular Biology International 37,133-140,1995
Hiroyuki Ohyama, Midori Hiramatsu, Norio Ogawa, Akitane Mori

Department of Neuroscience, Institute of Molecular and Cellular Medicine,
Okayama University Medical School, 2-5-1 Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute for Life Support Technology, Yamagata Technopolis Foundation,
Yamagata 683 Kurumanomae, Numagi, Yamagata 990, Japan

　　　　　　　　　　　　　　　　　　　　　　　　　　　　

　

Dr. HIROYUKI OHYAMA（Ph.D） in 1995.

Age-related difference in synaptosomal membrane fluidity
Biochemistry and Molecular Biology International 37,133-140,1995
Hiroyuki Ohyama, Midori Hiramatsu, Norio Ogawa, Akitane Mori

Department of Neuroscience, Institute of Molecular and Cellular Medicine,
Okayama University Medical School, 2-5-1 Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute for Life Support Technology, Yamagata Technopolis Foundation,
Yamagata 683 Kurumanomae, Numagi, Yamagata 990, Japan


岡山大学医学博士（分子細胞医学神経情報学）
徳島大学薬学修士（生物薬品化学）
大山博行（おおやまひろゆき）




大ベストセラー
光文社　カッパブックス
痴呆症（認知症）、アルツハイマーはもう怖くない
「脳を守る漢方薬」　医学博士　大山博行

脳の老化＝アルツハイマー病に光明。　最新科学で実証された漢方薬の効果があかされる。

　　　　


脳の老化とボケの関係をわかりやすく解説
認知症（痴呆症）、アルツハイマー病に対する最新情報満載
誰にでもできるボケ予防の６ヶ条を紹介


あなたも予備軍？６５歳以上の人のボケ（老人性痴呆＝認知症）発症率は７％、８５歳以上ではなんと２７％にも


BRAIN KAMPO

「　脳を守る漢方薬　」


最新科学で実証された「最新の漢方薬」とは、


漢方薬 No.1 ：老化の原因＝活性酸素を消去する

�@最新の漢方薬の強力な活性酸素（フリーラジカル）消去作用、最先端機器電子スピン共鳴装置ＥＳＲを用いた実験
ヒドロキシルラジカル、スーパーオキシドラジカルを消去する

漢方薬 No.2 ：記憶の中枢＝海馬と大脳皮質を守る

�A最新の漢方薬は、海馬、大脳皮質、小脳の過酸化脂質を減らす。
＊過酸化脂質：脳の老化の指標となる物質、この物質が減少していれば、脳の老化を抑制していることが示唆される。

漢方薬 No.3 ：ボケを防ぐだけでなく、長寿を約束する

�B最新の漢方薬は、誘導酵素ＳＯＤ活性を高める
老化促進モデルマウス（SAM-P8＝サムピーエイト）を用いた実験

漢方薬 No.4 ：脳の血管を守って、脳細胞死を遅らせる

�C最新の漢方薬の脳循環改善作用、脳代謝改善作用、遅発性神経細胞壊死DND改善作用
DND=Delayed Neuronal Death とは、

漢方薬 No.5 ：脳内神経伝達物質（ニューロトランスミッター）の合成を促す

�D最新の漢方薬のＣＡＴ（キャット）活性増強作用
ＣＡＴ（コリン・アセチル・トランスフェラーゼ）とは、

漢方薬 No.6 ：脳内の異常な興奮を鎮め、てんかん発作を抑える

�E最新の漢方薬の異常脳波（てんかん発作波）正常化作用
キンドリングキャットを用いた実験

漢方薬 No.7 ：神経突起を伸ばし、脳細胞の失われたネットワーク（記憶の痕跡）を再生する

�F最新の漢方薬の神経突起伸展作用、ラット初代培養神経細胞を用いた実験、
成長円錐　ＧＣ（Growth Cone）とは、
神経細胞毒（サイトカラシンＢ）を用いた実験
脳神経細胞のルーピング現象とは、

漢方薬 No.8 ：アルツハイマー病に特徴的な「空間認知障害」を防ぐ

�G最新の漢方薬の８方向放射状迷路装置を用いた実験
空間認知（Spatial Cognition）とは、

漢方薬 No.9：　漢方薬�@〜�Gの作用を併せ持つ


「自分で煎じて飲むことができ、副作用がない」


Produced by
Dr. HIROYUKI OHYAMA.（Ph.D）

Depertment of Neurochemistry, Institute for Neurobiology,
Okayama University Medical School
（ Director : Professor Akitane Mori ）
March 28, 1995

Reference

1) Effect of Kampo Medicine Preparations Using the Pathological Model of Dementia
Michihiro Fujiwara
Brain Research Conference for Japanese Kampo Medicine
pp.67-81,1990

2) Mixed Japanese Herbs and Age-Related Neuronal Functions
Midori Hiramatsu and Makiko Komatsu
Antioxidant Food Supplements in Human Health,edited by Lester Packer,
Midori Hiramatsu,Toshikazu Yoshikawa,
pp.412-428,1999

3) Effects of Japanese herbal medicine(TJ-960), on neuronal membrane fluidity of mice
Hiroyuki Ohyama,Midori Hiramatsu,Rei Edamatsu,Akitane Mori.
Magnetic Resonance in Medicine
6,279-281,1995

4) Antioxidant effect of TJ-960, a Japanese herbal medicine, against free radical-induced neuronal cell damage
Akitane Mori, Hajime Hamada, Hiroyuki Ohyama, Midori Hiramatsu, Seiichi Shinohara
International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects(ISNA),
pp.45-53.1996

5) Effect of TJ-960 on generalized seizure in amygdaloid kindled cats
Susumu Iizuka, Atsushi Ishige, Kyoji Sekiguchi, Akira Sugimoto, Kouichi Itoh, Masaki Aburada, Eikichi Hosoya, Eiichi Sugaya
Recent Advances in the Pharmacology of Kampo Medicines
pp.62-68,1988

6) Normalizing effect of SK commercial formula on cytochalasin-B
distorted neurites using primary cultured neurons of rat cerebeal cortex
Aiko Sugaya, Mitsutoshi Yuzurihara, Tadashi Tsuda, Eiichi Sugaya
J. Ethnopharmacol., 21: 193-199,1987.


7) Effect of Kampo Medicine Preparations Using the Pathological Model of Dementia
Michihiro Fujiwara
Brain Research Conference for Japanese Kampo Medicine
pp.67-81,1990


Copyright Kobunsha


　　




大ベストセラー
光文社　カッパブックス
痴呆症（認知症）、アルツハイマーはもう怖くない
「脳を守る漢方薬」　医学博士　大山博行
定価（本体８１９円＋税）

KAPPA BOOKS
ISBN4-334-00650-7
C0247 ￥819




1991
" THE KAMPO "



" KAMPO 漢方 "
How the Japanese Updated Traditional Herbal Medicine
Akira Tsumura, the Author　

About the Author :
Akira Tsumura has unique qualifications to brief us in the Western world
on the history and benefits of Japanese herbal medicine.
The pharmaceutical firm he heads has a long family tradition.
Tsumura, Inc. was founded by his grandfather, Jusha Tsumura,
and has diversified to become the leading supplier of herbal medicinals.
Sub-sidiaries in the United States are well-known distributors
of health and beauty care products.

At Tsumura, Inc. scientists using the latest technology
are testing the properties of various ancient Kampo medication.
In the Tokyo suburb of Tsuchiura, the firm has constructed a modern,
high-tech factory using robots for difficult research procedures.

The auther also has a warm appreciation of the needs
and attitudes of the American people.
His interest in Western culture has remained strong since he pursued a degree
in business management at the University of Michigan in Ann Arbor.
He has formed his own Dixieland jazz group in Japan, the Storyville Dandies !!!
His collection of vintage banjoes is the best in the world.　

" THE KAMPO "
1991

　　


資料提供
大山漢方堂薬局





KAMPO MEDICINE
Tradition Guiding Innovation



Report of the 100th Anniversary International
Kampo Symposium '93 Tokyo, Japan
9-10 April 1993



Medicines of Plant Origin
Patient Benefit and
Japanese Kampo Therapy 1991

　　　　　　

Program and Book of Abstracts

Report of an International Scientific
Workshop held in Bergen, Norway
31 May 1991

　


Recent Advances in the Pharmacology of
KAMPO MEDICINES
（JAPANESE HERBAL MEDICINES）
Proceedings of the Satellite Meeting on Kampo（Japanese Herbal） Medicines
of the 10th International Congress of Pharmacology,
Auckland, New Zealand, August 19-21, 1987

　　　

Basic and Clinical Studies of TJ-23 on Alzheimer's Dementia
Brain Research Conference for Japanese Kampo Medicine
1990

　　　　　　　　　　





資料提供
大山漢方堂薬局


The First International Conference on Senescence: The SAM Model
March 17-18,1994　Kyoto, Japon
PROCEEDINGS OF THE FIRST SAM KYOTO SYMPOSIUM

　

THE COUNCIL FOR SAM RESEARCH
Dept.of pathology chest disease res.inst.,
Kyoto university,Japan.1988


　　　　　　　　　　


This Issue Devoted to
Proceedings of the 18th Collegium Internationale
Neuro-Psychopharmacologicum Congress
Clinical Neuropharmacology

　　　

Collegium Internationale Neuro-Psychopharmacologium
18th C.I.N.P. CONGRESS
ACROPOLIS Convention Center,
Nice, France
June 28 - July 2, 1992


　　　　　　



資料提供
大山漢方堂薬局



　

Medicines of Plant Origin in Modern Therapy
from the 4th World Conference on Clinical Pharmacology, Prague 1989



A SYMPOSIUM REPORT
Published by Oxford Clinical Communications,
1989




　　

The English Guide to Medicinal Plants
and Kampo Formulae
1993

　　　

HERBAL MEDICINE : KAMPO,
Past and Present
1985


資料提供
大山漢方堂薬局


　


EUROPEAN JOURNAL OF PHARMACOLOGY
11th International Congress of Pharmacology
Amsterdam, The Netherlands
1-6 July, 1990




　　　　　　　　　　


Free Radicals in Brain Physiology and Disorders
An International Conference
Held in Celebration of the Retirement of Professor Akitane Mori

　　　　

August 4 and 5, 1995
International Convention Center PAMIR,
Tokyo,Japan

　　　　


資料提供
大山漢方堂薬局









「脳を守る漢方薬」
脳の老化とボケの関係をわかりやすく解説
認知症（痴呆症）、アルツハイマー病に対する最新情報満載
誰にでもできるボケ予防の６ヶ条を紹介



著者
医学博士　大山博行
Dr.HIROYUKI OHYAMA（Ph.D）
研究業績





漢方を現代病に活かす！大山漢方堂薬局
鍼灸を現代病に活かす！医学博士　大山博行
医学博士　大山博行
Dr.HIROYUKI OHYAMA（Ph.D）



大山宗伯東洋医学記念館



' sohhaku OHYAMA ' memorial
Institute of Natural Health Science

大山宗伯東洋医学記念館





Image of Ohyama Kampo

" KEIRAKU."



Kampo brewer



Medicine chests



Image of Ohyama Kampo



Prescription drawer chest found in pharmacies during the edo period



Kampo brewer made of metal



Used to grind crude drugs made of metal



Medicine chests

Image of Ohyama Kampo







Image of Ohyama Kampo




sohhaku OHYAMA memorial
Oriental Medicine
（Kampo medicines, Acupuncture & Moxibustion）
Museum



「1006」



「NAMBU]



「GOTOKU」



「YAKUKAN, YAKUTUBO & GOTOKU」

　

「Medicine Cases」

　　　

「Medicine Cabinets」

「Haribako」



Acupuncture & Moxibustion Box



Acupuncture & Moxibustion Box

「Kyubako」



「SAMURAI」

the edo period



「ATSUHIME」



「YAKUMI-TANSU」

Image of Ohyama Kampo

JAPANESE HERBAL MEDICINES



KAMPO MEDICINES



JAPANESE HERBAL MEDICINES



KAMPO MEDICINES

Image of Ohyama Kampo



　　　　　　　　　　



Reference

BIOCHEMISTRY & MOLECULAR BIOLOGY



A.S.B.M.B


　　　　　　









DR.HIROYUKI OHYAMA（Ph.D）

1)

Age-related difference in synaptosomal membrane fluidity

Hiroyuki Ohyama, Midori Hiramatsu, Norio Ogawa, Akitane Mori

Biochemistry and Molecular Biology International 37,133-140,1995

Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical

School, 2-5-1 Shikatacho, Okayama 700, Japan and *Division of Medical Science, Institute for Life

Support Technology, Yamagata Technopolis Foundation, Yamagata 683 Kurumanomae, Numagi, Yamagata 990, Japan


2)

Effect of Japanese herbal medicine(TJ-960) on neuronal membrane fluidity of mice

Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu, Akitane Mori

Magnetic Resonance in Medicine 6, 279-281, 1995


3)

Effect of Japanese herbal medicine(TJ-960), on aging

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori

Lipid-Soluble Antioxidants:Biochemistry and Clinical Applications.

pp.535-552,Birkhauser Verlag,Basel,1992


4)

Combined treatment of Japanese herbal medicine(TJ-960)with low dose of dipropylacetate increased the latent time for

pentylenetetrazol induced convulsion and decreased brain lipid peroxidation in mice.

Hiramatsu,M., Liu J, Edamatsu,R., Kadowaki,D., Hamada,H., Ohyama,H., Watanabe,S., Mori,A.

Neuroscience 18, 71-76,1992


5)
Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H., Yokoi,I., Kabuto,H., Ohyama,H., Mori,A., Teraoka,H., Komaru,N.

in: The SAM Model of Senescence (T.Takeda, ed.) pp.343-346,Elsevier Science B.V., Amsterdam, 1994


6)

Age-related changes in nitric oxide content and nitric oxide synthase activity

in senescence-accelerated mouse (SAM P8) brain

Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A., Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y., Nishijima,K.

in: Oxidative Stress and Aging (R.G.Cutler, L.Packer, J.Bertram, A.Mori, eds.)

pp387-391, Birkhauser Verlag, Basel, 1995


7)

UNESCO / Costam Workshop on Lipid-soluble Antioxidants in Biochemistry of Nutrition and Environmental Health

1991.9.21 (Malaysia)

Effect of Japanese herbal medicine(TJ-960), on aging

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori


8)

Society for Free Radical Research 1991.9027 (Paris)

Japanese herbal medicine(TJ-960) affected free radicals, SOD activity,

lipid peroxidation and neurotransmitter in aged rat brain

Midori Hiramatsu, Rei Edamatsu, Hiroyuki Ohyama, Akitane Mori


9)

5th International Congress on Oxygen Radicals 1991.11.18 (Kyoto)

Decreased membrane fluidity in rat synaptosomes induced by active oxygen species,

guanidino compounds and convulsants

Midori Hiramatsu, Rei Edamatsu, Hajime Hamada, Hiroyuki Ohyama, Akitane Mori


10)

5th International Congress on Oxygen Radicals 1991.11.20 (Kyoto)

Antioxidant effects of the extracts of gastrodia fleta bl. and uncaria rhynchophylla (MJQ) jacks

Jiankang Liu, Hajime Hamada, Hiroyuki Ohyama, Akitane Mori.


11)

The First International Conference on Senescence: The SAM Model 1994.3.17 (Kyoto)

Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H., Yokoi,I., Kabuto,H., Ohyama,H., Mori,A., Teraoka,H., Komaru,N.


12)

The First International Conference on Oxidative Stress and Aging 1994.3.25 (Hawaii)

Age-associated changes in nitric oxide (NO) content and nitric oxide synthase (NOS) activity

in senescence accelerated mouse (SAM P8) brain

Yokoi,I., Inada,K., Habu,H., Kabuto,H., Mori,A., Ohyama,H., Iwaya,K., Koyama,S., Nishijima,Y., Nishijima,K.


13)

International Conference on Bioradicals Detected by ESR Spectroscopy 1994.6.13 (Yamagata)

Effect of Japanese herbal medicine(TJ-960) on neuronal membrane fluidity of mice

Hiroyuki Ohyama, Midori Hiramatsu, Rei Edamatsu, Akitane Mori


14)

International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects (ISNA) 1995.6.21 (Beijin)

Antioxidant defenses of Japanese herbal medicine(TJ-960) , against free radical induced neural cell damages

Akitane Mori, Hajime Hamada, Hiroyuki Ohyama, Midori Hiramatsu, Seiichi Shinohara


Reference

1)

Mixed Japanese Herbs and Age-Related Neuronal Functions

Midori Hiramatsu and Makiko Komatsu

Antioxidant Food Supplements in Human Health,edited by Lester Packer,

Midori Hiramatsu,Toshikazu Yoshikawa,pp.412-428,1999

2)

Effects of Japanese herbal medicine(TJ-960), on neuronal membrane fluidity of mice

Hiroyuki Ohyama,Midori Hiramatsu,Rei Edamatsu,Akitane Mori.

Magnetic Resonance in Medicine 6,279-281,1995

3)

Antioxidant effect of TJ-960, a Japanese herbal medicine, against free radical-induced neuronal cell damage

Akitane Mori, Hajime Hamada, Hiroyuki Ohyama, Midori Hiramatsu, Seiichi Shinohara

International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects(ISNA),pp.45-53.1996

4)

Effect of TJ-960 on generalized seizure in amygdaloid kindled cats

Susumu Iizuka, Atsushi Ishige, Kyoji Sekiguchi, Akira Sugimoto, Kouichi Itoh, Masaki Aburada, Eikichi Hosoya, Eiichi Sugaya

Recent Advances in the Pharmacology of Kampo Medicines pp.62-68,1988

5)

Normalizing effect of SK commercial formula on cytochalasin-B distorted neurites using primary cultured neurons of rat cerebeal cortex

Aiko Sugaya, Mitsutoshi Yuzurihara, Tadashi Tsuda, Eiichi Sugaya

J. Ethnopharmacol., 21: 193-199,1987.

6)

Effect of Kampo Medicine Preparations Using the Pathological Model of Dementia

Michihiro Fujiwara

Brain Research Conference for Japanese Kampo Medicine pp.67-81,1990

7)

Estimation of nitric oxide and nitric oxide synthase activity in SAMP8 mouse brain

Habu,H.,Yokoi,I.,Kabuto,H.,Ohyama,H.,Mori,A.,Teraoka,H.,Komaru,N.

The SAM Model of Senescence(T.Takeda,ed.) pp.343-346,

Elsevier Science  B.V.,Amsterdam,1994

8)

Mixed Natural Antioxidants

Hiramatsu,M.

Food and Free Radicals,edited by Hiramatsu et al.

Plenum Press,New York,pp.113-117,1997



DR.HIROYUKI OHYAMA（Ph.D）


BIOCHEMISTRY & MOLECULAR BIOLOGY
HIGHER NERVOUS SYSTEM
KAMPO MEDICINE



Dr. HIROYUKI OHYAMA.（Ph.D）
1999

　　





　　　　　　



Reference

A.S.B.M.B



BIOCHEMISTRY & MOLECULAR BIOLOGY


　　　　　　　　　　







References １

(1) Whitehouse P.J., Price D.L. and Struble R.G. Alzheimer's disease and senile dimentia: loss of neurons in the basal forebrain. Science 215, 1237-1239, 1982.

(2) Price D.L., Whitehouse P.J. and Struble R.G. Alzheimer's diseases. Ann. Rev. Med. 36, 349-356, 1985.

(3) Appleyard M.E., Smith A.D., Wilcock G.K and Esiri M.M. Decreased CSF acetylcholinesterase activity in Alzheimer's disease. Lancet 20, 452, 1983

(4) Lovell M.A., Ehmann W.D., Butler S.M. and Markesbery W.R. Elevated thiobarbituric acid reactive substances and antioxident enzyme activity
in the brain in Alzheimer's disease. Neurology 45, 1594-1601, 1995.

(5)Mutisya E.M., Bowling A.B. and Beal M.F. Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J. Neurochem. 63, 2179-2184, 1994.

(6) Hensley K., Carney J.M., Mattson M.P., Aksenova M., Harris M., Wu J.F. and Floud R.A. A model for α-amyloid aggregation and neurotoxicity based
on free radical generation by the peptide: Relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 3270-3274, 1994.

(7) Kasai H. and Nishimura S. Hydroxylation of deoxyguanosine at the C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res. 12, 2137-2145, 1984.

(8) Shibutani S., Takeshita M. and Grollman A.P. Insertion of specific nases during DNA synthesis past the oxidation damage base 8-oxodG. Nature 349, 431-434, 1991.

(9) Cheng K.C., Cahill D.S., Kasai H., Nishimura S. and Loeb L.A. 8-Hydroxyguanine, an abundant form of oxidative DNA damage,
causes G→T and A→C substitutions. J. Biol. Chem. 267, 166-172, 1992.

(10) Prasad G.S., Lovell M.A. and Markesbery W.R. Increased nuclear DNA oxidation in the brain in Alzheimer's diseases. J. Neurochem. 71, 2034-2040, 1998.

(11) Sohal R.S., Agarwal S. and Sohal B.H. Oxidative stress and aging in the Mongolian gerbil (Meriones unquiculatus). Mech. Ageing and Dev. 81, 15-25, 1995.

(12) Asuncion J.G., Millan A., Pla R., Bruseghini L, Esteras A., Pallardo F.V., Sastre J. and Vina J. Mitochondrial glutathione oxidation correlates
with age-associated oxidative damage to mitochondrial DNA. FASEB J. 10, 333-338, 1996.

(13) Sastre J., Millan A., Asuncion J.G., Pla R., Juan G., Pallardo F., O'Conner E., Martin J.A., Droy-Refaix M.T. and Vina J. A Ginkgo biloba extract (EGb 761)
prevents mitochondrial aging by protecting against oxidative stress. Free Rad. Biol. Med. 24, 298-304, 1998.

(14) Mecocci P., Fano G., Fulle S., MacGarvey U., Shinobu L., Polidori M.C., Cherubini A., Vecchiet J., Senin U. and Beal M.F. Age-dependent increases
in oxidative damage to DNA, lipids, and proteins in human skeletal muscle. Free Rad. Biol. Med. 26, 303-308, 1999.

(15) Ciani E., Groneng L., Voltattorni M., et al. Inhibition of free radical production or free radical scavenging protects from the excitotoxic cell death mediated
by glutamate in cultures of cerebellar granule neurons., Brain Res. 728, 1-6, 1996.

(16) Dawson V.L. and Dawson T.M. Free radicals and neuronal cell death. Cell Death and Differentiation 3, 71-78, 1996.

(17) Pillot T., Drouet B., Queille S., Labeur C., Vandekerckhove J., Rosseneu M., Pincon-Raymond M. and Chambaz J.
The nonfibrillar amyloid _-peptide induces apoptotic neuronal cell death: Involvement of its c-terminal fusogenic domain. J. Neurochem. 73, 1626-1634, 1999.

(18) Herbison A.E., Augood S.J. and Slmonian S.X. Regulation of GABA transport activity and mRNA expression
by estrogen in rat preoptic ares. J. Neurosci. 15, 8302-8309, 1995.




References 2


1. Chartier-Harlin,M.C. et al. Early-onset Alzheimer's disease caused bymutations at codon precursor protein gene. Nature 353, 844-846 (1991).

2. Sherrington,R.et al. Cloning of a gene bearing missense mutations inearly-onset familial Alzheimer's disease. Nature 375, 754-760 (1995).

3. Rogaev,E.I. et al. Familial Alzheimer's disease in kindreds withmissense mutations in a gene on chromosome 1 related to the Alzheimer'sdisease type 3 gene. Nature 376, 775-778 (1995).

4. Borchelt,D.R. et al. Familial Alzheimer's disease-linked presenilin 1variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. Neuron 17,1005-1013 (1996).

5. Duff,K. et al. Increased amyloid beta42 (43) in brains of miceexpressing mutant presenilin 1. Nature 383, 710-713 (1996).

6. Nakano,Y.et al. Accumulation of murine amyloid beta42 with a gene-dosagedependent manner in PS1 'knock-in' mice. Eur.J.Neurosci. 11, 2577-2581(1999).

7. Iwatsubo,T. et al. Visualization of A?42 (43) and A?40 in senileplaques with end-specific A?monoclonals: evidence that an initiallydeposited species is A?42 (43). Neuron 13, 45-53 (1994).

8. Scheuner,D. et al. Secreted amyloid beta-protein similar to that in thesenile plaques of Alzheimer's disease is increased in vivo by thepresenilin a and 2
and APP mutations linked to familial Alzheimer'sdisease. Nature Med. 2, 864-870 (1996).

9. Wong,P.C. et al. Presenilin 1 is required for Notch and Dll1 expressionin the paraxial mesoderm. Nature 387, 288-292 (1997).

10. Davis,J.A. et al. An Alzheimer's disease-linked PS1 variant rescues thedevelopmental abnormalities of PS1-deficient embryos. Neuron 20, 603-609(1998).

11. De Strooper,B. et al. Deficiency of presenilin-1 inhibits the normalcleavage of amyloid precursor protein. Nature 391, 387-390 (1998).

12. Wolfe,M.S. et al. Two transmembrane aspartates in presenilin-1required for presenilin endoproteolysis and gamma-secretase activity.Nature 398, 513-517 (1999).

13. Guo,Q.et al. Alzheimer's presenilin mutation sensitizes neural cells toapoptosis induced by trophic factor withdrawal
and amyloid?-peptide:involvement of calcium and oxyradicals. J.Neurosci. 17, 4212-4222 (1997).

14. Guo,Q.et al. Increased vulnerability of hippocampal neurons toexcitotoxic necrosis in presenilin-1 mutant knock-in mice. Nature Med. 5,101-106 (1999).

15. Sidrauski,C.et al. The unfolded protein response: an intracellularsignalling pathway with many surprising features. Trends in Cell Biol. 8,245-249 (1998).

16. Tirasophon,W. et al. A stress response pathway from the endoplasmicreticulum to the nucleus requires
a novel bifunctional proteinkinase/endoribonuclease (Ire1p) in mammalian cells. Genes Dev. 12,1812-1824(1998).

17. Wang,X-Z.et al. Cloning of mammalian Ire1 reveals diversity in the ERstress responses. EMBO J. 17, 5708-5717 (1998).

18. Katayama, T. et al. Presenilin-1 mutations downregulate the signalling pathway of unfolded protein response. Nature Cell Biol. in press (1999).

19. Iwatsubo, T. et al. Purification and characterization of Lewy bodiesfrom the brains of patients with diffuse Lewy body disease. Am.J.Pathol.148, 1517-1529 (1996).

20. DiFiglia,M. et al. Aggregation of huntingtin in neuronal intranuclearinclusions and dystrophic neurites in brain. 　Science 277, 1990-1993(1997).



References 3

1) Raff, M. C., Barres, B. A., Burne, J. F., Coles, H. S., Ishizaki, Y., and Jacobson, M. D. (1993)
Programmed cell death and the control of cell survival: lessons from the nervous system. Science, 262:695-700.

2) Purves, D.(1988) "Body and Brain" Harverd University Press.

3) Levi-Montalcini, R. And Angeletti, P. (1968)
Nerve growth factor, Pysiol. Rev., 48:534-569.

4) Cohen, S. And Levi-Montalcini, R. (1956)
A nerve growth-stimulating factor isolated from snake venom. Proc. Natl. Acad Sci. USA, 42:571-574.

5) Johnson, E. M., Gorin, P. D., Brandeis, L. D. And Pearson, J. (1980)
Science, 210:916-918.

6) Smeyne, R. J., Klein, R., Schnapp, A., Long, L. K., Bryant, S., Lewin, S. A. and Barbacid, M. (1994)
Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF. Nature, 368:246-248.

7) Davies, A. M., Enokido, Y. and Wyatt, S.(1999)
Paradigms of neurotrophic factor action in regulating neuronal survival in the developing nervous system. Taniguchi Symposium, in press.

8) Davies, A. M., Bandtlow, C., Heumann, R., Korsching, S., Rohrer, H. And Thoenen, H. (1988)
Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature, 326:353-358.

9) Wyatt, S. And Davies, A. M.(1993)
Regulation of expression of mRNAs encoding the nerve growth factor receptors p75 and trkA in developing sensory neurons. Development, 119:635-648.

10) Buchman, V. L., and Davies, A. M.(1993)
Different neurotrophins are expressedand act in a developmental sequence to promote the survival of embryonic sensory neurons. Development, 118: 989-1001.

11) Davies, A. M. (1997)
Neurotrophin switching: where does it stand? Curr. Opin. Neurobiol.,7:110-118.

12) Verdi, J. M. And Anderson, D. J. (1994)
Neurotrophins regulate sequential changes in neurotrophin receptor expression by sympathetic neuroblasts.Neuron, 13:1359-1372.

13) Wang, H. And Tessier-Lavigne, M.(1999)
En passant neurotrophic action of and intermediate axonal target in the developing mammalian CNS. Nature, 401;765-769.

14) Davies , A. M. and Wright, E. M. (1995) Neurotrophin autocrine loops. Curr. Biol., 5:723-726.

15) ElShamy, W. M., Fridvall, L. K. and Ernfors, P.(1998)
Growth arrest failure, G1 restriction point override, and S phase death of sensory precursor cells in the absence of neurotrophin-3.Neuron, 21:1003-15

16) Enokido, Y., Wyatt, S. and Davies, A. M. (1999)
Developmental changes in the response of trigeminal neurons to neurotrophins: influence of birthdate and the ganglion environment. Development, 126:4365-4373.

17) Ma, Q., Fode, C., Guillemot, F. and Anderson, D. J.(1999)
NEUROGENIN1 and NEUROGENIN2 control two distinct waves of neurogenesis in developing dorsal root ganglia. Genes & Dev., 13:1717-1728.

18) Ma, Q., Chen, Z., del Barco Barrantes, I., de la Pompa, J. L. and Anderson, D. J. (1998)
Neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron, 20:469-82

19) Fode, C., Gradwohl, G., Morin, X., Dierich, A., LeMeur, M., Goridis, C. and Guillemot, F. (1998)
The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode-derived sensory neurons. Neuron, 20:483-94

20) O'Connor, R. and Tessier-Lavigne, M.(1999)
Identification of maxillary factor, a maxillary process-derived chemoattractant for developing trigeminal sensory axons. Neuron, 24:165-178.

21) Lumsden, A. G., and Davies, A. M. (1983)
Earliest sinsory nerve fibers are guided to peripheral targets by attractants other than nerve growth factor. Nature,306:786-788.

22) Tessier-Lavigne, M., and Placzek, M. (1991)
Target attraction: are developing axons guided by chemotropism? Trends Neurosci., 14:303-310.

23) Blasschke, A. J., Staley, K. and Chun, J.(1996)
Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development, 122:1165-1174.





BIOCHEMISTRY & MOLECULAR BIOLOGY
HIGHER NERVOUS SYSTEM
KAMPO MEDICINE

Dr. HIROYUKI OHYAMA.（Ph.D）

　　






Age-related difference in synaptosomal membrane fluidity
Biochemistry and Molecular Biology International 37,133-140,1995
Hiroyuki Ohyama, Midori Hiramatsu, Norio Ogawa, Akitane Mori

Department of Neuroscience, Institute of Molecular and Cellular Medicine,
Okayama University Medical School, 2-5-1 Shikatacho, Okayama 700, Japan
and *Division of Medical Science, Institute for Life Support Technology, Yamagata Technopolis Foundation,
Yamagata 683 Kurumanomae, Numagi, Yamagata 990, Japan

Dr. HIROYUKI OHYAMA（Ph.D） in 1995.


資料提供：

東洋医学記念館
Oriental Medicine Museum