Lecture 8 Brain and nervous system
Thiamine lackWernicke's encephalopathy
Lack of niacin Pellagra
Uremic coma
Diabetic coma
DehydrationNaKCa
Electrolyte imbalance
Poisoning
Poison
Cerebrovascular accident
low CBF
Orthostatic fainting
Shock
D I C
Adams-Stokes syndrome
Cardiac infarction
Low O 2
Anemia
Lungdisease
Excessive injectionof Insulin
Inslinoma Low blood of sugar
Hepatic coma High ammonia
prostaglandin D 2 Sleep center
( medial preoptic area )
prostaglandin E 2Arousal center( A back hypothalamus )
Pituitary gland
Mesencephalic reticular formation
Medullary reticular formation
ThalamusHypothalamus
Cerebral cortex
Metabolic acidosis
日 本 アメリカ
Frequency difference of Japan-U.S. of serotonin transportation body gene multi type
SS type 68.2Obedience
Depolarization
SS type 18.8
LS type30.1
LS type 48.9AggressiveIndependent
LL type 32.3Too aggressive
LL type 1.7
100
80
60
40
20
0
%Fre
qu
en
cy o
f ge
ne
mu
lti typ
e
(%)
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
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!
5-HTT
0.0
50.0
100.0
L/ L L/ S S/ S
Frequency of gene polymorphism of character ( Number of investigations=264)
Independent type.Strong against stress
Uneasiness and the stress are sensitive
DRD4
0.0
50.0
100.0
R 2~4 のみ 5 7R ~ 有
Seeking a new thingStrong against stress
Multi type of serotonin transporter
S/S type
Tendency as which as many as four dopamine receptor multi types are the same
Caucasian type
Japanese type
Japanese type
Yamakawa, M. et al. “Serotonin transporter polymorphisms affect human blood glucose control” Biochem Biophys Res Commun. 334(4), 2005, 1165-71
only
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
DRD4(Dopamine D4 receptor)
State of excitation
always
Stabilityorientation
5-HTTLPR
ReceptorSerotonin
Aggressive, Independent
Sensitive, Nervous
L is transcript revitalization ten times S
By 「 The mind has been understood here 」Kosuke oki
The mad cow disease is discovered from cannibals' Kuru disease
Sheep
The cow was made to eat sheep's
scrap meat
Cow
Eating the hamburg steak with which the nerve mixes
Kuru disease Scrape. Spongiform encephalopathyCroitsfeld Creutzfeldt-Jakob disease. Mad cow disease
Croitsfeld Creutzfeldt-
Jakob disease
Cannibals in New Guinea
The Kuru disease to the chimpanzee
Milk
is
safe
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
Nobel Prize in Medicine in 1997
Cannibals
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
Higher-order, structural
change and proliferation
of Prion
Nobel Prize inMedicine in 1997 and
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
70
75
80
85
90
95
Life e
xpe
ctan
cy
/life ex
pe
ctan
cy w
itho
ut
de
me
ntia
(%)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
認知症認知症
見当識なし
Checkpoints where the dementia is doubted
Not understanding my age.
Not understanding a familiar interpersonal relationship.
Dangerous sign
Forgetting that should be noted
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
A personal experience of the previous state is forgotten for a moment. The same thing is repeated many times in a series of conversation
How of dementia symptom to appear
Main symptom
hallucination
Delusion
Confusionperplexity
excitement
Other intellectual disabilities
emotional disorder
Impaired orientationEasy angry
Not computable
Symptom in surrounding
Defect of memory
Creation of talk
Not writing
Not perception
認知症
= Dementia by cerebral infarction and brain hemorrhage
Cause of Dementia
Disease can be treated Chronic subdural hematoma Normal pressure hydrocephalus Brain tumor False dementia Dementia symptom by medicine
Vascular dementia
Degenerative nervous disease (Alzheimer's disease. etc )
Relation of dangerous rate of lifestyle and cerebrovascular dementia
Non factor 11 factor + - - - - 14.4
- + - - - 2.7
- - + - - 2.9 - - - + -
2.5 - - - - + 2.2
2 factors 5.3 ~42.23 factors 14.5~ 115.64 factors 42.6 ~284.95 factors + + + + + 613.4
not leisure active
Past of hypertension
notexerciseactive
Head injury loses senses
Nonparticipation to the medical examination
Risk(odds ratio)
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
Red
is a b
rain activity
Red
is a b
rain activity
Left brain
Left brain
Left brain
Right brainRight brain
Right brain
Brain when easy calculation problem is solved fast
Brain when complicated calculation is solved
Brain when book is read aloud
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
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 infarctionRisk of folic acid intake and cerebral infarction(follow-up survey of 43,732 men and 14 years)(follow-up survey of 43,732 men and 14 years)
0
0.5
1
1.5
Low High
Folic acid intake
Relative
risk
He K, Merchant A, Rimm EB, Rosner BA, Stampfer MJ, Willett WC, Ascherio A. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men (2004) Stroke 35(1) p.169-74
相対危険度
Method of calculating diversity score of food intake
Meat, Seafood, Eggs, Milk, Soybean and processed soy product, Brightly colored vegetable, Sea weed, Potato, Fruit, Oils and fats
Each food group“Eat almost every day” 1 point "Do not eat" is 0 point.*The maximum becomes ten points.
0
0.5
1
1.5
1~3 4~8 5~10
Relative risk of decrease in higher-order life function of diversity score each crowd of food intake
point
When various foods are taken, it is not easy to become Dementia
point point
Osamu KUMAGAI, “Relation of Variety of food intake in regional home senior person and higher-order life depression”, 『 The journal of Japanese public health 』 , 50(12), 2003.12 p.1117-24
Protective efficacy by fishBordeaux, 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
1 time a week
Someties
Not at all
Eat meat 1 time or more everyday
Rate of appearance
It is the effect none even if it takes it as supplement
The vegetable and the fruit prevent Alzheimer
Chicago : 1993-2000. 815 of 65 years old or more is pursued average 3.9 years later
Rotterdam : 1993-2000. 5395 of 55 years old or more is pursued average 6 years later
Intakes of vitamin E under the meal are 70% low from few crowds of a lot of crowds that are
Intakes of vitamin C & E under the meal are 43% low from few crowds of a lot of crowds that are
-20
-10
0
10
20
Food that prevents Dementia (1995→2002)
Brightly colored vegetables
Beans Seafood
Am
ou
nt o
f inc
reas
e
an
d d
ecre
as
e
Potato
(%)
Healthy Japan 21,”Tentative nearest results value in healthy Japan 21 to target value (2005)”, Available from <http://ml-www.kenkounippon21.gr.jp/kenkounippon21/ugoki/houkoku/pdf/0410mokuhyou_zanteiti.pdf>, (accessed 2007-11-4)
As for the content of the folic acid, in the analysis table, availability is different
Structure of folic acids
PteridineAminobenzoic aci
d
Mono-glutamic acid type folic acid
Polyglutamic acid type folic acid
Folic acid in multivitamin and enriched food
Folic acid in natural food
Polyglutamic acid type folic acid
Mono-glutamic acid type folic acid or
Folic acid (Pteroylpolyglutamic acid)
(Monoglutamic folic acid: polyglutamic folic acid = 1:2)
The number of homo cysteines increases due to folic acid shortage
AdenosylHomo cysteine
アデノシルメチオニン
メチオニン
Homocysteine
Tetrahydrofolic acid
Dihydrofolic acid
5 、 10-methyleneTetrahydrofolic
acid5-MethylicTetrahydrofolic
acid
Shistationin
Cysteine
CBS
B 6
CLB 6
MTHFR B 2
BHMTMS
B 12ベタイン
N,N-Gemetilgrishin
痴呆Infarction DementiaExamining TT type
Folicacid
Methionine
Adenosyl
methionine
Betaine
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 → DNACpG island S adenosyl homo cysteine.The activity leaf acid lack after DNA methyl transferase (five kinds) generates the egg is measured due to 14C methylic radical uniting decrease to DNA.
RFC-1 : 1 reduction folic acid transportation body multi type
Digestion, absorption of folic acid, Digestion, absorption of folic acid,
and resolution of Porigltamil radicaland resolution of Porigltamil radical
amylase
Protease
Conjugase
Blood
Folic acids
Mono-glutamic acid type folic acid
Mono-glutamic acid type folic acid
Mono-glutamic acid type folic acid
Protein Folic acid
Starch, Protein, Folic acid
Polyglutamic folic acid
Small intestines epithelial cell
methylenetetrahydrofolate
100g当たり140mg
This folic acid reinforced plan and eating folic acid amounts in the This folic acid reinforced plan and eating folic acid amounts in the United States (DFEs)United States (DFEs)
I Obligated synthetic folic acids of the grain processed foods such as bread and cereals (every 100g) to be strengthened in the United States in 1998
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
Eating folic acid this amount Folic acid under mealAmount of synthetic
folic acid
Folic acid in food that exists naturally
Synthetic folic acid in enriched food
Absorption factor of 50%
Absorption factor of 85%
When the folic acid is insufficient, it becomes an acknowledgment syndrome
Rise of homo cysteine in blood
Cardiac infarction
DementiaCerebral infarction
Do
n’t like
vegetab
les
Co
ns
titutio
n(g
en
e
)
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.
*p < 0.05, **p<0.01
(n)0
5
10
15
(82) (129) (39)
****
CC CT TT
Even if the folic acid, VB6, and the VB12 intake are fulfilled, the density of
the person of the TT type of the serum total homocysteine is high
The entire object person
(74) (113) (36)
****
Those who fulfill folic acid Recommendation amount
(54) (81) (28)
**
Folic acid ・B6 ・ B12 those fulfill recommendation amount
(mol/l)
As for the diabetic, folic acid shortage becomes the patient of a 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 multi type with the risk in the limitation food with a lot of
acknowledgment syndromes (Alzheimer's disease and apoplexy).acknowledgment syndromes (Alzheimer's disease and apoplexy).
0
50
100
150
200
Comparison Diabetic
Ris
k o
f A
lzh
eim
er
100
165
Arvanitakis Z. et al. “Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function” Arch Neurol. 61(5), 2004, 661-6
0
1
2
3
4
5
6
0
1
2
3
4
5
6
7
8
Unnoticed Cerebral infarction
Homocysteine (nmol/ml) Homocysteine (nmol/ml)
**
Cerebral infarction that notices symptoms
The cerebral infarction increases by a factor of 5.5-7.5 when the homo cysteine is high
*
*** ***
<6.8 6.9-8.1 8.2-10.2 ≥10.3
<6.8 6.9-8.1 8.2-10.2 ≥10.3
Amount of homocysteineAmount of
homocysteine
Disco
very frequ
ency o
f cerebral in
farction Araki A. et al. “Association between plasma homocysteine concentrations and asympt
omatic cerebral infarction or leukoaraiosis in elderly diabetic patients” Geriatrics and Gerontology International. 3(1), 2003, 15-23
Disco
very frequ
ency o
f cerebral in
farction
22
23
24
25
26
27
20
25
30
35Achievement test1 MMSE
Achievement test 2
few middle lot few middle lot
Amount of homocysteine (nmol/ml) Amount of homocysteine (nmol/ml)
* **
The intelligence decrease begins before the syndrome of acknowledgment when the homo cysteine is high
Score Score
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 C677T gene polymorphism and the total density of serum ho
mocysteine ( Dementia senior perwon at Yokufu-Kai )
Folic acidFolic acid Total homocysteine Total homocysteine
* *
(mol/l)
0
10
20
30
40
*
(nmol/l)
* p<0.005 (vs. TT)CC CT TT
0
10
20
30
40
50
Seniordementia
Young women
Middle and advance women
Young women
Middle and advance women
Such high!
Such low!
Seniordementia
If the person of the TT type also takes the folic acid of 400μg every day, it is safe
316:1210-1216 (2004)
Gene polymorphism and folic acid blood levelFolic acid administering Folic acid administering
Den
sity of fo
lic acid
in b
loo
d
HIRAOKA,KATO,SAITO,YASUDA, KAGAWA
Of Japanese
a day a day
Preliminary examinationNumber of 300
Load examinationNumber of 100
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
(weeks)
Acknowledgment level point after density of senior citizen of plasma folic acid and three stages and three years of folic acid intakePrevention of acknowledgment syndrome of start
-1.05
-0.9
-0.75
-0.6
-0.45
-0.3
-0.15
0
0.15
0.3
0.45
0.6
Ch
ang
e in
ackno
wled
gm
ent level
po
int
Elderly person : 321 ( 60-74 )
<20nmol/L <339μg/d
20-30 339-523nmol/L μg/d
>30nmol/L >523μg/d
Density of plasma folic acid
Folic acid intake amount/day
******
****** P<0.0001
** P<0.01
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
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
Min
i men
tal test score
Serum folic acid ( ng/ml)
Lim
its are 4Nan
o
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)
The folic acid of 140μg for every 100g is compulsorily added to bread and cereals in 1998 and it makes significant progress in the United States. A nursing necessary senior citizen decreaseGreat 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.
Healty nourishment investigation in US. Serum folicacid
0
2
4
6
8
10
12
14
16
1988-1994 1999-2000 2001-2002
Investigation year
Ser
um fol
ic a
cid
ng/m
l
It increases the serum folic acid because of US citizen's food folic acid strengtheningGanji V. et al. : J. Nutrition 136: 153-158 (2006)
Folic acid
addition to
bread
Healty nourishment investigation in US. Homoshistin densitytransition
0
2
4
6
8
10
12
1988-1994 1999-2000 2001-2001
Investigation year
Ser
um H
omos
hist
in d
ensi
tyUS citizen's food: decreasing the homo cysteine because of the folic acid strengthening. Ganji V. et al. : J. Nutrition 136: 153-158 (2006)
Folic acid addition to bread
Role of folic acid and Food that contains a lot of folic acids
Functions of folic acids Main supply source of folic acids
Necessary amount of folic acids
Alzheimer type dementia prevention
Arteriosclerosis prevention
The risk of embryo's nerve tube hypoplasia is decreased Spinach
Roasted laverGreen tea Extracted material
Broccoli
Cabbage
Egg
(a day)
for pregnant woman
The Ministry of Health, Labour and Welfare
(5th ed Food composition table)
per
(Mami FUKUSHIMA, Yasuo KAGAWA et at all)
“Sakado” Folic acid project
1. The lack of the folic acid intake is measured with the homo cysteine
2.The constitution with the folic acid is an insufficient easily is judged by the inheritance
Meal investigation (questionnaire) and guidance
It improves it judging the lifestyle that becomes an acknowledgment syndrome easily
Gene multi type judgment applicant
October 2ed
: Individual guidance about result
September 4th
: Explanation-Agreement-Collecting blood
Cooking practice and physical exercise
After half a year, inspecting again the homocysteine
The acknowledgment syndrome and the cerebral infarction can be prevented regardless of the constitution
The density of the serum folic acid rose
MTHFR C677T
according to gene multi type
Den
sity
of s
erum
folic
aci
d
(ng
/ml)
Guidance before
Guidance after
before
after before
before
p<0.0001 p<0.05 p<0.0001 p<0.01
0
5
10
15
20
25
0
5
10
15
20
25CC CT TTn=27 n=27 n=11
after after
Folic acid and constitution of diabetic
Meal, movement, brain gymnastics
The acknowledgment syndrome can be prevented by the folic acid, the balance food, the exercise, and the brain activity
Bad lifestyle, Folic acid lack and depolarization Appearance of diseaseB
A
Co
nscio
us b
y th
e gen
etic test
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