Lecture 8 Brain and nervous system
Cerebrovascular accident Adams-Stokes syndrome Cardiac infarction low CBF Orthostatic fainting Pellagra Shock Thiamine lack Wernicke's encephalopathy DIC Anemia Lung disease Low O２ Lack of niacin Uremic coma Metabolic acidosis Cerebral cortex Excessive injection of Insulin Inslinoma Hepatic coma prostaglandin D２ Dehydration Low blood of sugar Thalamus Hypothalamus High ammonia Sleep center Pituitary gland Mesencephalic reticular formation Medullary reticular formation Arousal center （A back hypothalamus） Na K Ca Electrolyte imbalance Poisoning （medial preoptic area ） prostaglandin E２ Diabetic coma Poison
Frequency difference of Japan-U. S. of serotonin transportation body gene multi type Frequency of gene multi type （ ） ％ ％ 100 80 ＬＳ type 30. 1 60 40 ＳＳ type 68. 2 Obedience 20 0 Depolarizat ion ＬＬ type 1. 7 The Japanese educates kindly and severely to the group and the individual because the character to which it is the same as mild others and relieves it ＬＬ type 32. 3 Too aggressive ＬＳ type 48. 9 Aggressive Independe nt ＳＳ type 18. 8 The education, the resource, and the target of composure are given and it teaches to an independent, independent student of the United States freely. Teacher, please shut up!
Frequency of gene polymorphism of character （Number of investigations=264） Tendency as which as many as four dopamine receptor multi types are the same Multi type of serotonin transporter Japanese type Seeking a new thing Strong against stress Caucasi an type S/S type Independe nt type. Strong against stress Uneasines s and the stress are sensitive Japa nese type only Yamakawa, M. et al. “Serotonin transporter polymorphisms affect human blood glucose control” Biochem Biophys Res Commun. 334(4), 2005, 1165 -71
More objective than the psychological test. When the fearful expression is seen, the amygdaloid nucleus (right picture red) that shows feelings of likes and dislikes acts. It reacts to the Japanese and the amygdaloid nucleus reacts to a lot of S/S types that are sensitively Inherited difference of emotion by functional, magnetic resonance image method Serotonin transporter S type L type ○ ○ Hariri AR, Weinberger DR. “Imaging genomics” Br Med Bull. 65, 2003, 259 -70
DRD 4 (Dopamine D 4 receptor) State of excitation always Stability orientation
5 -HTTLPR L is transcript revitalization ten times S Aggressive, Independent Sensitive, Nervous Receptor Serotonin By 「The mind has been understood here」 Kosuke oki
The mad cow disease is discovered from cannibals' Kuru disease Cannibals in New Guinea Sheep The Kuru disease to the chimpanzee The cow was made to eat sheep's scrap meat Cannibals Kuru disease Scrape. Spongiform encephalopathy Croitsfeld Creutzfeldt. Jakob disease. Mad cow disease Croitsfeld Creutzfeldt. Jakob disease Cow ilk M s i e f sa Eatin g th steak e hambur g wi the ne th which rve m ixes Nobel Prize in Medicine in 1997 Yasuo KAGAWA, “Dr. Stanley B. Prusiner, Advocator of Prion theory 1997 Nobel Prize in Medicine”, 『The Japanese journal of nutrition』, 322, 1998. 1 p. 26 -31
The agents responsible for mad cow disease is a protein of not the microorganism but Prion. It acts on the Prion in normal person's brain and it changes it into no To Prion Nobel Prize in Medicine in 1997 and Higher-order, structural change and proliferation of Prion Yasuo KAGAWA, “Dr. Stanley B. Prusiner, Advocator of Prion theory 1997 Nobel Prize in Medicine”, 『The Japanese journal of nutrition』, 322, 1998. 1 p. 26 -31
It is Japan that in the world with a lot of dementias and bedridden Life expectancy /life expectancy without dementia （％） Remainder of one's life without 77 -years old man's dementia Eiji YANO, “The statistics tells. From average life span to Healthy life span. Its challenge and international comparison” 『The Journal of the Japanese medical association』, 123(6), 2000. 3 p. 823 -8
Checkpoints where the dementia is doubted 認知症 Forgetting that happens with aging The name of the actor who reflects in the television cannot be recalled. It has forgotten to buy one carelessly though it went shopping. Sentences are being written, the Chinese character cannot be recalled, and it often uses a dictionary Forgetting that should be noted A personal experience of the previous state is forgotten for a moment. The same thing is repeated many times in a series of conversation Dangerous sign 見当識なし Not understanding a familiar interpersonal relationship. Not understanding my age.
How of dementia symptom to appear excitement emotional disorder Easy angry Defect of memory Not perception Impaired orientation Main symptom Not computable perplexity Not writing hallucination Creation of talk Other intellectual disabilities Confusion Delusion Symptom in surrounding
Cause of Dementia 認知症 Degenerative nervous disease (Alzheimer's disease. etc ) Vascular dementia = Dementia by cerebral infarction and brain hemorrhage Disease can be treated Chronic subdural hematoma Normal pressure hydrocephalus Brain tumor False dementia Dementia symptom by medicine
Relation of dangerous rate of lifestyle a nd cerebrovascular dementia not Head injury Nonparticipation Past of leisure exercise loses to the medical hypertension senses examination active Non factor １ factor ＋ － ＋ － － － ２ factors ３ factors ４ factors ５ factors ＋ ＋ ＋ Risk (odds ratio) 1 － － 14. 4 － － － 2. 7 ＋ － － 2. 9 － ＋ － 2. 5 － － ＋ 2. 2 5. 3～ 42. 2 14. 5～ 115. 6 42. 6～ 284. 9 ＋ ＋ 613. 4 Kiyotaro KONDO, “Lifestyle and dementia （Featuring : lifestyle and disease-Effectiveness of preventive medicine and the actual patient guidance）」, 『The journal of the Japanese medical association』, 119(7), 1998. 4 p. 935 -41
To prevent the acknowledgment syndrome, the simple calculation is read aloud early Brain when complicated calculation is solved Brain when book is read aloud i ty a b Red i rai n s act i vi t y a b Red i rai na s c ti v Brain when easy calculation problem is solved fast Left brain Right brain Working of the brain when an easy calculation problem is solved as soon as possible is shown. It is understood that a lot of places of a right and left brain move actively Left brain Right brain Working of the brain when working on the complicated calculation is shown. The prefrontal region and times of a lower head of a left brain work. A right brain doesn't work Working of the brain when the book is read aloud is shown. More much more places work than reading it silently by a right and left brain. It is understood the faster the reading speed is the prefrontal region, the more to work
Risk of folic acid intake and cerebral infarction (follow-up survey of 43, 732 men and 14 years) Relative risk Low High Folic acid intake He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Folate, vitamin B 6, and B 12 intakes in relation to risk of stroke among men (2004) Stroke 35(1) p. 169 -74
Meat, Seafood, Eggs, Milk, Soybean and processed soy product, Brightly colored vegetable, Sea weed, Potato, Fruit, Oils and fats 相対危険度 various foods are taken, When it is not easy to become Dementia Each food group “Eat almost every day” １ point "Do not eat" is 0 point. *The maximum becomes ten points. point Method of calculating diversity score of food intake point Relative risk of decrease in higherorder life function of diversity score each crowd of food intake Osamu KUMAGAI, “Relation of Variety of food intake in regional home senior person and higherorder life depression”, 『The journal of Japanese public health』, 50(12), 2003. 12 p. 1117 -24
Protective efficacy by fish Bordeaux, FRANCE 1, 674 of 68 years old or more is pursued seven years later. 170 people became dementias. 135 people became Alzheimer sooner or later Eat fish 1 time or more everyday (stndard) 1 time a week Someties Not at all Eat meat 1 time or more everyday 1 time a week Someties Not at all Rate of appearance
The vegetable and the fruit prevent Alzheimer Chicago : 1993 -2000. 815 of 65 years old or more is pursued average 3. 9 years later Intakes of vitamin E under the meal are 70% low from few crowds of a lot of crowds that are Rotterdam : 1993 -2000. 5395 of 55 years old or more is pursued average 6 years later Intakes of vitamin C & E under the meal are 43% low from few crowds of a lot of crowds that are It is the effect none even if it takes it as supplement
Food that prevents Dementia （１９９５→２００２） Amount of increase and decrease （％） Brightly colored vegetables Beans Seafood Potato Healthy Japan 21, ”Tentative nearest results value in healthy Japan 21 to target value (2005)”, Available from <http: //mlwww. kenkounippon 21. gr. jp/kenkounippon 21/ugoki/houkoku/pdf/0410 mokuhyou_zanteiti. pdf>, (accessed 2007 -11 -4)
Structure of folic acids Folic acid (Pteroylpolyglutamic acid) As for the content of the folic acid, in the analysis table, availability is different Mono-glutamic acid type folic acid Polyglutamic acid type folic acid Folic acid in multivitamin and enriched food Folic acid in natural food (Monoglutamic folic acid: polyglutamic folic acid = 1: 2) Pteridine Aminobenzoic acid Mono-glutamic acid type folic acid or Polyglutamic acid type folic acid
The number of homo cysteines increases due to folic acid shortage Methionine メチオニン Adenosyl アデノシル メチオニン methionine N, N-Gemetilgrishin BHMT MS B１２ Betaine ベタイン Adenosyl Homo cysteine Dihydrofolic acid Tetrahydrofolic acid Folic acid 5 -Methylic Tetrahydrofolic acid Homocysteine 5、10 -methylene Tetrahydrofolic acid CBS MTHFR B２ B６ Shistationin Examining TT type Infarction Dementia 痴呆 CL B６ Cysteine
From the folic acid to the reaction of DNA methylation • • ① Transportation body small intestines and → Folmiltetorahidoro folic acid → Metenil tet rahydrofolic acid → Metirentetorahidoro folic acid of folic acid ② Metirentetorahidoro folic acid + NADH→ methylenetetrahydrofolate reductase → Metilt etorahidoro folic acid + NAD • ③ homo cysteine + Metiltetorahidoro folic acid → methionine synthetase → methionine + tetrahydrofolic acid • ④ Methylate + of C methionine + ATP→ S adenosylmethionine → DNACp. G island S adenosyl homo cysteine. The activity leaf acid lack after DNA methyl transferase (five kinds) generates the egg is measured due to 14 C methylic radical uniting decrease to DNA.
Digestion, absorption of folic acid, and resolution of Porigltamil radical Starch, Protein, Folic acid Protein Folic acid amylase Protease Folic acids Mono-glutamic acid type folic acid Polyglutamic folic acid RFC-1 ： 1 reduction folic acid transportation body multi type Small intestines epithelial cell Blood Conjugase Mono-glutamic acid type folic acid methylenetetrahydrofolate
This folic acid reinforced plan and eating folic acid amounts in the United States (DFEs) I Obligated synthetic folic acids of the grain processed foods such as bread and cereals (every 100 g) to be strengthened in 100 g当たり States in 1998 the United 140 mg Eating folic acid this amount Folic acid under meal Folic acid in food that exists naturally Synthetic folic acid in enriched food Amount of synthetic folic acid Absorption factor of 50% Absorption factor of 85% The correction coefficient of this 1. 7 originates in the ratio in which the presumption availability of a synthetic folic acid in food is divided by the presumption average availability of eating sericulture
When the folic acid is insufficient, it becomes an acknowledgment syndrome Constitution (gene ） Don’t like vegetables Rise of homo cysteine in blood Dementia Cerebral infarction Cardiac infarction It is not worrying if it notes it for a moment because this gene polymorphism is a small difference of the gene between normal people.
Even if the folic acid, VB 6, and the VB 12 intake are fulfilled, the density of the person of the TT type of the serum total homocysteine is high ** (mmol/l) ** ** ** * * 15 10 5 0 (82) (129) (39) The entire object person CC CT TT (74) (113) (36) Those who fulfill folic acid Recommendation amount (54) (81) (28) (n) Folic acid・B 6・ B 12 those fulfill recommendation amount *p < 0. 05, **p<0. 01
As for the diabetic, folic acid shortage becomes the patient of a multi type with the risk in the limitation food with a lot of acknowledgment syndromes (Alzheimer's disease and apoplexy). Risk of Alzheimer 165 100 Arvanitakis Z. et al. “Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function” Arch Neurol. 61(5), 2004, 661 -6
The cerebral infarction increases by a factor of 5. 5 -7. 5 when the homo cysteine is high Unnoticed Cerebral infarction *** Cerebral infarction that notices symptoms *** * Amount of homocysteine <6. 8 6. 9 -8. 1 8. 2 -10. 2 ≥ 10. 3 Homocysteine (nmol/ml) Discovery frequency of cerebral infarction ** Araki A. et al. “Association between plasma homocysteine concentrations and asymptomatic cerebral infarction or leukoaraiosis in elderly diabetic patients” Geriatrics and Gerontology International. 3(1), 2003, 15 -23
The intelligence decrease begins before the syndrome of acknowledgment when the homo cysteine is high Achievement test１ MMSE * Achievement test 2 ** Score few middle lot Amount of homocysteine (nmol/ml) Araki A. et al. “Plasma homocysteine and cognitive function in elderly patients with diabetes mellitus” Geriatrics and Gerontology International. 3(2), 2003, 86 -92
Density of serum folic acid according to acknowledgment syndrome senior citizen‘ MTHFR C 677 T gene polymorphism and the total density of serum homocysteine （Dementia senior perwon at Yokufu-Kai） (nmol/l) Folic acid Su 40 30 * Total homocysteine (mmol/l) 50 ch Such lo 40 w ! 30 20 10 0 0 ! 20 10 high Young women Middle and advance women CC Senior dementia CT * * Young women TT Middle and Senior advance dementia women * p<0. 005 (vs. TT)
he person of the TT type also takes the folic acid of 400μg every day, it is safe Gene polymorphism and folic acid blood level Folic acid administering a day Density of folic acid in blood AOKA, KATO, SAITO, YASUDA, KAGAWA a day Cerebral infarction and dementia's worries are a little if 400 νg intakes of the folic acid in case of the type as well as the CC type and the CT type Of Japanese Preliminary examination Number of 300 Load examination Number of 100 (weeks) ３１６：１２１０－１２１６ （２００４）
Acknowledgment level point after density of senior citizen of plasma folic acid and three stages and three years of folic acid intake Prevention of acknowledgment syndrome of start Change in acknowledgment level point **** Elderly person : 321（60 -74） ** ** ** P<0. 01 **** P<0. 0001 Density of plasma folic acid Folic acid intake amount/day <20 nmol/L <339μg/d 20 -30 339 -523 nmol/L μg/d >30 nmol/L >523μg/d Tucker KL. et al. “High homocysteine and low B vitamins predict cognitive decline in aging men: the Veterans Affairs Normative Aging Study” Am J Clin Nutr. 82(3), 2005, 627 -35
The density of the serum folic acid falls sharply and the intelligence of the level 80 years old per four Nano mg/ml falls sharply Limits are 4 Nano Mini mental test score Intelligence test of 471 of 87 years old on average. The correlation of MMSE and the density of the serum folic acid is extremely significant r=0. 36(p<0. 0001) Serum folic acid （ ng/ml) Tettamanti M. et al. “Low folate and the risk of cognitive and functional deficits in the very old: the Monzino 80 -plus study” J Am Coll Nutr. 25(6), 2006, 502 -8
The folic acid of 140μg for every 100 g is compulsorily added to bread and cereals in 1998 and it makes significant progress in the United States. A nursing necessary senior citizen decrease Great decrease in cardiac infarction. The deformed child of the nerve also : to 1/8. The folic acid recommendation amount has increased to about twice that of Japan, too.
It increases the serum folic acid because of US citizen's food folic acid strengthening Ganji V. et al. : J. Nutrition 136: 153 -158 (2006) n io dit li Fo id ac c ad to b a re d
US citizen's food: decreasing the homo cysteine because of the folic acid strengthening. Ganji V. et al. : J. Nutrition 136: 153 -158 (2006) Fo lic aci da ddi tion to b rea d
Role of folic acid and Food that contains a lot of folic acids Functions of folic acids The risk of embryo's nerve tube hypoplasia is decreased Main supply source of folic acids (Mami FUKUSHIMA, Yasuo KAGAWA et at all) per Spinach Roasted laver Green tea Extracted material Arteriosclerosis prevention Broccoli Alzheimer type dementia prevention Cabbage Egg (5 th ed Food composition table) Necessary amount of folic acids (a day) The Ministry of Health, Labour and Welfare for pregnant woman
“Sakado” Folic acid project September 4 th October 2 ed ：Explanation-Agreement-Collecting blood ：Individual guidance about result １．The lack of the folic acid intake is measured with the homo cysteine Gene multi type judgment applicant 2. The constitution with the folic acid is an insufficient easily is judged by the inheritance Meal investigation (questionnaire) and guidance Cooking practice and physical exercise After half a year, inspecting again the homocysteine It improves it judging the lifestyle that becomes an acknowledgment syndrome easily The acknowledgment syndrome and the cerebral infarction can be prevented regardless of the constitution
The density of the serum folic acid rose Density of serum folic acid （ng/ml) MTHFR C 677 T 25 25 according to gene multi type CC n=27 20 n=11 befo after re p<0. 0001 befo after re p<0. 01 10 5 n=27 15 10 TT 20 15 CT 5 0 Guidance before after p<0. 0001 0 befo after re p<0. 05
The acknowledgment syndrome can be prevented by the folic acid, the balance food, the exercise, and the brain activity A B Meal, movement, brain gymnastics Bad lifestyle, Folic acid lack and depolarization Appearance of disease Conscious by the genetic test Folic acid and constitution of diabetic
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