B i ish
Jou nul
o
Nui i ion
(1992),
68,
409420 409
Changes in neu o ansmi e le els associa ed wi h he de iciency
o
some essen ial amino acids in he die
BY
JOSE
L.
VENERO, ANTONIO
J.
HERRERA, ALBERT0 MACHADO
AND JOSEFINA CAN0
Depn amen
o
de Bioy hica,
B oma nlogia
y
Toxicologia, Uni e sidnd
de
Se illa,
C/
P~nj.
Ga cia
Conzulez sln, 41012-Se illu, Spain
(Recei ed
I1
Feb ua y
1991
-Accep ed
23
Augus
1991)
The con en s o dopamine (DA) and se o onin (5-HT) and hei me aboli es we e measu ed in a
subs an ia nig a and co pus s ia um ollowing die a y changes, including es ic ion o p o ein con en
(low-p o ein die ; LPD) and he con en s
o
se e al la ge neu al amino acids (isoleucine, leucine,
me hionine, phenylalanine, yp ophan and aline) o
25
d. The LPD p oduced an inc ease in he
concen a ion o y osine (TYR) in he wo egions o he b ain s udied. This e ec was also obse ed
wi h all amino acid de iciencies s udied excep o aline in he subs an ia nig a, yp ophan in he
s ia um and phenylalanine in bo h egions. Likewise, he concen a ion o 5-hyd oxyindolace ic acid (5-
HIAA),
he main me aboli e o
5-HT,
inc eased in he subs an ia nig a bu no in he s ia um a e
LPD, as well as wi h
all
he amino acid de iciencies s udied, wi h he excep ion o yp ophan de iciency.
In
his case he e
was
a
d ama ic e ec on all componen s o he se o onine gic sys em, wi h dec eases
in he concen a ion o yp ophan (TRP
;
p ecu so ),
5-HT
and 5-HIAA. This beha iou clea ly shows
an in e ela ionship be ween p ecu so (TRP) a ailabili y and
5-HT
syn hesis and me abolism. Wi h
aline de iciency, dopamine gic and se o onine gic sys ems demons a ed opposi e e ec s in he
subs an ia nig a and he co pus s ia um, and he beha iou
o
he wo monoamines was also opposi e
wi hin each s uc u e. The signi icance o hese changes is discussed.
Subs an ia nig a
:
S ia um
:
Malnu i ion
:
Monoamines
The amino acid composi ion o a p o ein, pa icula ly he essen ial amino acid po ion, is
c ucial o nu i ion. Mos die a y p o eins, especially hose de i ed om ege able sou ces,
a e poo in some essen ial amino acids (Schoe ield
&
Boo h, 1983). The in ake
o
hese
essen ial amino acids is impo an in such unc ions as p o ein syn hesis and g ow h (S e n
e
ul.
I976
:
Wes
&
Kempe , 1976). Se e al amino acids a e also in ol ed in biogenic amine
biosyn hesis, while o he s a e hemsel es neu o ansmi e s.
The impac o p o ein malnu i ion on he b ain has been examined a di e en s ages
o li e, p ima ily du ing de elopmen and ma u a ion (Winick
&
Rosso, 1973; Winick,
1989). The e ec
o
loading o de iciency o essen ial amino acids such as yp ophan,
phenylalanine o y osine has also been e alua ed (Mille
e
al.
1976, 1977a; Du ing
e
al.
1989; Wes e ink
&
De V ies, 1991) in an e o o de e mine he esul ing impac on he
syn hesis and concen a ion
o
neu o ansmi e subs ances (Fe ns om
&
Wu man, I97
1
;
Mille
e
al.
1977h). Howe e , li le a en ion has been ocused on he compa a i e e ec
o di e en essen ial amino acid de ici s and neu o ansmi e syn hesis in adul s. Taking
in o accoun he eal possibili y o malnu i ion a some ime du ing he adul s age, we
s udied i s e ec on some aspec s
o
b ain unc ion.
The p esen s udy was designed o de e mine he e ec o a die a y de iciency in some
o
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
410
J.
L.
VENERO
AND
OTHERS
he essen ial amino acids on he le el o biogenic amines ac ing as neu o ansmi e s in
di e en a eas o he cen al ne ous sys em. The e ec o he biogenic amines se o onin
(5-HT)
and dopamine (DA), hei espec i e p ecu so s yp ophan (TRP) and y osine
(TYR), and hei me aboli es 5-hyd oxyindolace ic acid (5-HIAA, 3,4-dihyd oxy-
phenylace ic acid (DOPAC), 3-me hyoxy y amine (3-MT) and homo anillic acid
(HVA)
was in es iga ed, because i is known ha hese neu o ansmi e s a e in luenced by di e en
amino acids, especially yp ophan and phenylalanine, as p ecu so s o indolamines and
ca echolamines espec i ely. A he same ime, hey a e anspo ed ac oss he blood-b ain
ba ie by he la ge neu al amino acid anspo sys em,
so
hey mus compe e wi h aline,
leucine, isoleucine, y osine and me hionine o access o he ca ie -binding si e (Pa d idge,
1983). Fo hese easons hese amino acids we e selec ed. The wo egions selec ed o he
s udy we e he co pus s ia um and he subs an ia nig a o he a because hey a e
ex emely ich in neu o ansmi e con en , allowing measu emen
o
changes in hei
concen a ions, and because in human pa ien s wi h a ious neu ological diso de s changes
in biogenic amine le els ha e been desc ibed in hese a eas. Thus, Pa kinson’s disease is
associa ed wi h a degene a ion o dopamine gic cell bodies o he pa s compac
o
he
subs an ia nig a (Hi sch
e al.
1988) and a dec ease in DA concen a ion in he s ia um
(Ma sden, 1982). The nig o-s ia al sys em has also been epo ed o be in ol ed in o he
neu ological diso de s. Fo ins ance, Hun ing on’s disease is associa ed wi h se e e
degene a ion and cell
loss
in he co pus s ia um, whe e e e en neu ons o all he s ia al
neu o ansmi e s a e a ec ed (Enna
e
al.
1977; Penney
&
Young, 1982; Scheel-K uge ,
1986). Likewise, he e is degene a ion
o
he melanin-pigmen ed neu ons in he subs an ia
nig a in Alzheime ’s disease (Mann
e
al.
1982).
The e ec s we e s udied in adul a s: (1) ed on he s anda d con ol die (CD); (2) ed
on a low-p o ein die supplemen ed wi h
all
essen ial amino acids (LPD; his die ha ing
all he nu i ional equi emen s ecommended by Na ional Academy o Sciences (1978))
;
(3)
ed on a low-p o ein die -supplemen ed wi h all essen ial amino acids excep one.
The indings suppo he hypo hesis ha a de iciency in some o hese amino acids
induces changes in biogenic amine le els. In some cases, he e is a dec ease in he
concen a ion
o
dopamine o se o onin ha could exace ba e an incipien pa hological
disease ela ed
o
hese le els.
EXPERIMENTAL METHODS
Animuls and ea men
Thi y- wo male Wis a a s weighing 150-200
g
and bo n in ou labo a o y we e used.
Animals we e housed in eigh g oups ( ou a s pe cage) unde a 12 h ligh -da k cycle.
They we e ed
on
a s anda d comme cial die (Panlab) un il adminis a ion
o
he
expe imen al die s: CD, LPD and LPD wi hou one o he essen ial amino acids o be
es ed. The composi ion o hese die s was as ollows.
CD.
This con ained (g/kg) 180 lac albumin, 220 suc ose, 440 dex in, and
1
10 a , wi h
he emainde o he die composed
o
i amins and mine als ( a die co ec o i amin and
mine als, Incole -1
;
Inco esa, Leon). The o al amino acid composi ion is shown
in
Table
1.
LPD.
This was an isoene ge ic die con aining (g/kg)
5
lac albumin, 270 suc ose, 560
dex in, and
110
a , as well
as
lysine 14.6, h eonine
5.0,
a ginine 14.9, his idine 5.4,
me hionine 4.8, isoleucine
5,
leucine 7.5, phenylalanine
8.0,
yp ophan 2.6, aline 6.0, wi h
he emainde
o
he die composed o i amins and mine als. De ails
o
he amino acid
composi ion o LPD a e shown in Table 1.
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
EFFECT
OF
DIET IN NEUROTRANSMITTER
LEVELS
41
1
Table
1.
Amino
acid
composi ion
(glkg)
o
con ol
die
(CD)
and
low-p o ein die
(LPD)
-
~
Amino acids CD
LPD
Aspa ic acid 14
5
04
Glu amic acid 16
1
04
Aldnine 32
01
A ginine
21
14 9
Cys eine 11 8 03
Phenyldlanine
80
82
Glycine 54
01
His idine
56
01
Isoleucine 12
7
53
Leucine 20
7
80
Lyaine 21
2
15
2
Me hionine 19
48
P oline 28
01
Se ine 89
02
Ty osine 88
03
Th eonine
10
I
53
Valine 86 62
ASpd dglne I9 3
05
Glu d nine
71 02
__
T yp ophan
99
29
-
~~
Expe imen
a1
die s
Six di e en expe imen al die s we e p epa ed. The composi ion o each die was iden ical
o
LPD
excep o he omission
o
me hionine, isoleucine, leucine, phenylalanine,
yp ophan o aline.
Th oughou he s udy all a s we e gi en ood and wa e
ad
lib.
The die s we e ed o
25
d be o e each expe imen . The ood in ake was eco ded daily and co ec ed o spillage.
All animals we e decapi a ed be ween
10.00
and 11.00 hou s and he whole b ain was
quickly emo ed. The mesencephalon was di ided in o wo pa s, wi h an incision om he
en al side a he caudal bo de eminence unning pe pendicula o he long axis o he
mesencephalon. The wo subs an ia nig as we e hen easily iden i ied, and dissec ed ee
o
he su ounding issue, including he en al egmen al a ea (A
lo).
The esul ing po ion
was ozen in liquid ni ogen, as was a simila ly-p epa ed po ion o he s ia um. The o al
ime-pe iod equi ed o isola ion o each po ion was less han
3
min.
Measu emen
o
biogenic
amines
Analyses we e pe o med by means o a high-pe o mance liquid ch oma og aph equipped
wi h a Kon on
420
pump wi h elec ochemical de ec ion (Bioanaly ical Sys em, LC-4B).
Measu emen o he biogenic amines and hei me aboli es was pe o med acco ding o
me hods desc ibed in de ail elsewhe e (Vene o e
al.
1989).
Typical expe imen al
ch oma og ams a e shown in Fig.
1.
Ch oma og ams we e eco ded
on
a Me ck-Hi achi
in eg a o (model
D-2000).
Accu a e in eg a ing op ions we e equi ed o in eg a ing
TYR
in
bo h subs an ia nig a and s ia um, and DOPAC in he s ia um. In o de o ob ain
an adequa e in eg a ion o bo h me aboli es, a ail op ion was chosen o in eg a ing
TYR,
and a pe pendicula d op o DOPAC.
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
412
J.
L.
VENERO
AND
OTHERS
4
2
I
3
Fig.
1.
Ch oma og ams o dopamine
(DA),
se o onin (5-HT) and hei me aboli es om:
(A)
a s ia al issue
a e 25 d on a low-p o ein die ;
(B)
a
s ia al issue a e 25 d on a yp ophan-de icien die .
J,
injec ion peak;
1,
y osine; 2, dopamine; 3,
3,4-dihyd oxyphenylace ic
acid
:
4,
5-hyd oxy-3-indolace ic acid;
5,
3-me h-
oxy y amine;
6,
5-HT;
7,
homo anillic acid;
8,
yp ophan.
Fo
de ails
o
die s, see pp.
41041
1
and Table
1.
S a ly ical analysis
Biogenic amine con en s om animals ed on CD and LPD we e compa ed using S uden ’s
es . Da a om LPD and he di e en amino acid-de icien die s we e analysed by means
o one-way analysis o a iance
(ANOVA).
Obse ed mean di e ences we e e alua ed
using he Sche ee es (pa ame ic es ). Food in ake and body-weigh
loss
we e compa ed
using S uden ’s
es .
RESULTS
Food
in ake and hody-weigh
loss
The e we e no signi ican di e ences in ood in ake (g/animal pe d) be ween CD and LPD
and he di e en expe imen al die s:
CD
16.7
(SE
1.4), LPD and expe imen al die s 15.2
(SE 1.4). The e we e no di e ences in body-weigh
loss
(YO):
CD 10.6
(SE
0.9),
LPD and
expe imen al die s
13.2
(SE
2.1). The ac ha all ea men s led o a ce ain deg ee o body-
weigh loss could be a ibu ed o he low pala abili y o he die s. This is suppo ed by he
inding ha he highes loss a e was eco ded du ing he i s week o he ea men s.
Howe e , om day
8
o
25
(be o e dea h) he espec i e body-weigh s emained almos
unchanged.
E ec
o
LPD
on
neu o ansmi e
le els
The e we e no signi ican changes in he se o onine gic sys em, excep o 5-HTAA which
inc eased in he subs an ia nig a wi h LPD when compa ed wi h CD
(38.0%;
P
<
0.01
;
Table 2). Mo eo e , li le change was ound in he concen a ion o 5-HT in he wo egions
a e LPD, bu he e was an inc ease in he subs an ia nig a and a dec ease in he s ia um.
Wi hin he dopamine gic sys em, an inc ease
in
he concen a ion o TYR a e LPD was
seen in bo h s uc u es (42.2% in he subs an ia nig a, 25.4% in he s ia um;
P
<
0.01;
Tables
3
and
5).
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
EFFECT
OF
DIET IN NEUROTRANSMITTER
LEVELS
413
Table 2
E lec s
o
a iou die s on he concen a ion (ng/g we issue)
o
se o onin
(5-
HT)
and
i s
me aboli es in he subs an ia nig a
o
a s
HIAA
SEM
18
7, d 23)
(The combined
SEM
and d o each compound we e TRP
SEM
54 2, d 21, 5-HT
SEM
48 7, d 21, 5-
~ ~ ~
~~~~~~____~
~
-~
~~~~~~
______________~
Die ? TRP 5-HT 5-HIAA
___.-
~
__
______~~____
~~
CD 3386 4 2018 4 452 4
LPD 35189 2164 9 624 51
LPD de icien in
Isoleucine 3344
I
2001 8 582 4
Leucine 3727 9 1811 5** 6408
Me hionine 3312 8 17037** 6277
Phenylalanine 3344 3 18195* 6423
T yp ophan 1731 9** 1051 4** 250
I**
Valine 3526 9 17145** 5757
__
~ ~
-~
____
~
~~~_____
~~-~
~ ~ ~ ~
__
________~.
~~
____~
CD, con ol die , LPD, low-p o ein die , TRP, yp ophan, 5-HIAA, 5-hyd oxyindolace ic acid
Mean alues o amino acid-de icien die s we e signi ican ly di e en om hose o LPD (one-way analysis
o a iance ollowed by Sche ee es )
*
P
<
0
05,
**
P
<
0
01
Fo
de ails
o
die s, see pp 41041
1
and Table
I
Mean alue o LPD was signi ican ly di e en om ha o CD (S uden ’s
es )
1
P
<
0
01
Table 3.
E ec s
o
a ious die s on he concen a ion (ng/g we issue)
o
dopamine
(DA)
and i s me aboli es in he subs an ia nig a
o
a s
(Thecombineds~~andd o eachcompound
we e:TYRs~~212.1,d 21; DASEM 18.1,d 21;DOPAC
SEM
3.6.
d
21
;
3-MT
SEM
2.6, d 21
;
HVA
SEM
46,
d
21)
.
.~
-
~~~
--.--
.
-
___
___~._____..._____
~~
.~
~~
~-
~
~~-_____
Die ? TY R DA DOPAC
3-MT
HVA
CD
6083.2
7105 102.2 51.1 130.5
LPD 8655,6$ 769.7 98.0 47.8 138.7
___________.____
~~
__.__~~
LPD de icien
in:
Isoleucine 8053.0 572.7**
I1
1.7
56.9
109.8*
Leucine 10803.6** 649.0*
139.8**
50.0 131.7
Me hionine
8
767.4 762.7 115.7 51.5 124.3
T yp ophan 7 905.2 584.9**
110.7
53.7 131.5
Valine 7
108*
838.8 139.5** 5 .6 178.9**
Phenylalanine 6813.5** 550.2**
80.8
509 119.1
~
.~
~~
___
__~
~~~
~~~.~.____~
~~
~~ ~~ ~ ~
___.______~~__~
CD, con ol die ; LPD, low-p o ein die : TYR, y osine; DOPAC,
3.4-dihyd oxyphenylace ic
acid; 3-MT,
3-
Mean alues o amino acid-de icien die s
we e
signi ican ly di e en om hose o LPD (one-way analysis
1-
Fo
de ails o die s,
see
pp. 41041
1
and Table
I.
Mean alue o LPD
was
signi ican ly di e en om ha o CD (S uden ’s
es ):
$
P
<
04,)l.
me hoxy y dmine
;
HVA, homo anillic acid.
o
a iance ollowed by Sche ee es ):
*
P
<
0.05,
**
P
<
0.01.
Subs an ia nig a
sdeucin de ici .
This de ici had no e ec on he se o onine gic sys em. Wi hin he
dopamine gic sys em his de ici was associa ed wi h a dec ease in he concen a ions
o
DA
(-25.6%;
P
<
0.01) and HVA
(-21.0%;
P
<
0.05) compa ed wi h ha
o
LPD
(Table
3).
Leucine de ici .
Compa ed wi h LPD his de ici induced a dec ease in he concen a ion
o
5-HT (-16.3%,
P
<
0.01;
Table 2). The 5-HIAA: 5-HT a io was also inc eased
compa ed wi h ha ob ained wi h LPD (20.6
%).
Wi h espec o he dopamine gic sys em,
15
NUT
68
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess

414
J.
L.
VENERO
AND
OTHERS
he e was an inc ease
in
he concen a ions o TYR and DOPAC when compa ed wi h
hose ob ained wi h LPD (24.8 and 41.8
YO
o TYR and DOPAC espec i ely;
P
<
0.01
;
Table 3), whe eas DA concen a ions dec eased
(-
15.6
YO,
P
<
0.05
;
Table 3). The e lux
o DA, quan i ied as D0PAC:DA a io (Al a
e al.
1987), was also inc eased compa ed
wi h ha ob ained wi h LPD (69.2
YO).
Me hionine dejici .
This de ici caused
a
dec ease
In
he concen a ion o 5-HT when
compa ed wi h ha ound wi h LPD (-21.3
YO;
P
<
0.01
;
Table 2). Howe e , he e lux o
5-HT, measu ed as 5-HIAA:5-HT a io, inc eased wi h espec o LPD (27.5%).
No
s a is ical change was de ec ed in he dopamine gic sys em a e his de ici .
Phenylulunine de ici .
De ici o his amino acid caused a dec ease in he concen a ion o
5-HT when compa ed wi h ha ob ained wi h LPD
(-
15.9%;
P
<
0.05;
Table
2).
The
u no e o 5-HT, measu ed as 5-HIAA
:
5-HT a io, inc eased compa ed wi h ha ound
wi h LPD
(20.6 YO).
Wi hin he dopamine gic sys em he e was a signi ican dec ease in he
concen a ions o TYR (-21.2%;
P
<
0.01) and DA (-28.4%;
P
<
0.01)
compa ed wi h
hese ob ained wi h LPD (Table 3).
T yp ophan de ici .
This de ici had a d ama ic e ec on all componen s o he
se o onine gic sys em, showing a ela ionship be ween p ecu so a ailabili y and 5-HT
syn hesis. Thus, he e was
a
dec ease in he concen a ions o TRP
(-
50.7
YO),
5-HT
(-
5
1.4
"/o)
and 5-HIAA
(-
59.9
YO
;
P
<
0.0
I)
compa ed wi h hose ob ained wi h LPD
(Table
2).
Wi h espec o he dopamine gic sys em his de ici dec eased he concen a ion
o DA wi h espec o LPD (-24.0%;
P
<
0.01
;
Table 3); he D0PAC:DA a io was
inc eased compa ed wi h ha ob ained wi h LPD (46.1
%).
Valine de$ci .
This de ici caused
a
dec ease in he concen a ion o 5-HT when compa ed
wi h ha o LPD
(-20.8%,
P
<
0.01)
(Table
2).
Wi hin he dopamine gic sys em he
concen a ions
o
DOPAC and HVA we e inc eased compa ed wi h hose ob ained wi h
LPD
(42.3
YO
o DOPAC and 28.9
YO
o HVA;
P
<
O.Ol),
and ha o TYR dec eased
(-
17.8
O/O
;
P
<
0.05
;
Table
3).
Mo eo e , he DOPAC
:
DA a io was inc eased compa ed
wi h ha ound wi h LPD (30.7%).
S ia um
Isoleucine
de ici .
This de ici had
no
e ec on he se o onine gic sys em. Wi hin he
dopamine gic sys em, only HVA concen a ion dec eased compa ed wi h ha ob ained
wi h LPD
(-
32.9
YO
;
P
<
0.01
;
Table
5).
Leucine de ici .
De ici o leucine caused a dec ease in he concen a ion o 5-HT
compa ed wi h ha ob ained wi h LPD
(-
24.8
YO,
P
<
0.05
;
Table
4).
In
he dopamine gic
sys em he e was an inc ease in he concen a ions o TYR and DOPAC compa ed wi h
hose ound wi h LPD (83.4
YO
o TYR and 42.7
YO
o DOPAC;
P
<
O.Ol),
and a dec ease
in HVA
(
-
10.8
%
;
P
<
0.0
1
;
Table 5); he DOPAC
:
DA a io was inc eased compa ed
wi h ha wi h LPD (31.2%).
Me himine de ici .
De ici o me hionine caused only a dec ease in he TRP concen a ion
compa ed wi h ha ob ained wi h LPD
(-25.6%,
P
<
0.01)
in he se o onine gic sys em
(Table 4). In he dopamine gic sys em he e was a dec ease in he concen a ions
o
TYR
(-
27.6
YO,
P
<
0.05) and HVA
(-
22.7
YO,
P
<
0.01)
when compa ed wi h hose o LPD
(Table
5).
Phenylalanine de ici .
This de ici only had an e ec on he dopamine gic sys em. Thus,
he e was
a
dec ease in he concen a ions o TYR
(-33.7
%,
P
<
0.01)
and HVA
compa ed wi h hose o LPD (-21.3Y0,
P
<
0.01;
Table
5).
These esul s we e
accompanied by an inc eased DOPAC
:
DA a io wi h espec
o
LPD (25.0
%).
T yp ophan
de ici .
This de ici , as o he subs an ia nig a, had a ma ked in luence on all
he componen s
o
he se o onine gic sys em. Thus, he e was a dec ease in he
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
EFFECT
OF
DIET
IN
NEUROTRANSMITTER
LEVELS
415
Table
4.
E ec s
o
a ious die s
on
he concen a ion
(ng/g
we issue)
o
se o onin
(5-HT)
and i s me aboli es
in
he s ia um
o
a s
(The combined
SEM
and d o each compound we e: TRP
SEM
134.6,
d
21; 5-HT
SEM
39.7,
d
22;
5-HIAA
SEM
10.5,
d
24)
~~
.
~~~
._
~
~ ~
___~_________________
Die TRP 5-HT 5-HIAA
.~
~~
____~
~
~__.___._______~
CD
4623.7 1056.4 28
1.8
LPD
4677.3 9 10.6 301.6
LPD de icien in
:
Isoleucine
3994.4 1131.2 3 15.2
Leucine
4961.1 684.3* 256.9
Me hionine
3476.6** 1021.5 295.2
Phenylalanine
4437.9 843.5 288.6
T yp ophan
2440.6** 5663** 135,9**
Valine
4895.7 1169,2* 290.2
~____~
~____~.~~
~~~~~ ~
~~~ ~
~________.____.~~.~-~.-~.~~-
~~
CD, con ol die
:
LPD, low-p o ein die
:
TRP, yp ophan
;
5-HIAA, 5-hyd oxyindolace ic acid.
Mean alues o amino acid-de icien die s we e signi ican ly di e en om hose o LPD (one-way analysis
Fo
de ails o die s, see pp.
41041
I
and Table
1.
o
a iance ollowed by Sche ee es ):
*
P
<
0.05;
**
P
<
0.01,
Table
5.
E lec s
o
a ious die s
on
he concen a ion
(ng/g
we issue)
o
dopumine
(DA)
and i s me aboli es in he s ia um
o
u s
(The combined
SEM
and d o each compound we e: TYR
SEM
376.4,
d
21
;
DA
SEM
396.7,
c
24:
DOPAC
SEM
83.2, d
23;
3-MT
SEM
22.8, d
24;
HVA
SEM
25.8,
d
23)
~~ ~~ ~~~~
~.
~~~~~ ~ ~~ ~~
.~
~___
_____.~~..~..~_____~
~
Die TYR DA DOPAC 3-MT
HVA
~~
~~ ~~~
~.
CD
5 950.8 12 220.4 1903.4 547.1 889.7
LPD
7466.7$ 12599.9 1989.3 549.9 882.0
LPD de icien in
:
Isoleucine
6
646.0 10548.2 2170.4 505.9 591.2**
Leucine
13
693,0**
13
606.6 2839.8** 640.1 786.0**
Me hionine
5402.3
1
1208.6 21 17.7 649.9 681,8**
Phenylalanine
4944.6** 10844.9 2112.5 518.1 694.3**
T yp ophan
6682.4 1228
1.0
1987.2 582.7 586.0**
Valine
7 502.
I
83990** I482.8** 412.2** 414.5**
~~~ ~
-
~~~~~
~ ~ ~~
~.
~~ ~~
CD, con ol die ; LPD, low-p o ein die ; TYR, y osine; DOPAC, 3,4-dehyd oxyphenylace ic acid; 3-MT,
3-
Mean alues o amino acid-de icien die s we e signi ican ly di e en om hose
o
LPD (one-way analysis
Fo
de ails o die s, see pp.
41041
1
and Table
1.
Mean alue o LPD was signi ican ly di e en om ha o CD (S uden 's
c
es ):
$
P
<
0.01.
me hoxy y amine
;
HVA, homo anillic acid.
o
a iance ollowed by Sche ee es )
:
*
P
<
0.05,
**
P
<
001.
concen a ion o TRP
(-474
YO),
5-HT
(-
55.1
%)
and
5-HIAA
(-
55.1
YO;
P
<
0.01
;
Table
4).
In con as o he se o onine gic sys em, in he dompamine gic sys em he e was
only
a
dec ease in he
HVA
concen a ion, compa ed wi h ha ob ained wi h
LPD
(-
33.5
%
;
P
<
0.01) (Table
5).
Vulinp de ici .
Wi hin he se o onine gic sys em, only an inc ease in 5-HT concen a ion
compa ed wi h LPD was de ec ed
(28.3
'4
;
P
<
0.05
;
Table
4).
In
he dopamine gic sys em
he e ec was opposi e o ha seen in he subs an ia nig a ollowing his de ici . Thus,
excep TYR, he concen a ions o all componen s o his neu o ansmi e sys em we e
15-2
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
416
J.
L.
VENERO
AND
OTHERS
dec eased wi h espec o LPD: DA
-33.3
%,
DOPAC -25.4%,
3-MT
-25.0% and
HVA
-53.0%
(P
<
0.01
;
Table 5).
DISCUSSION
We ha e s udied he changes in neu o ansmi e con en in adul animals ed on die s
de icien in some essen ial amino acids o a sho pe iod o ime (25 d). This si ua ion may
be ound in some pa hological condi ions and may be impo an in olde pe3ple. Thus, wi h
age he e is an inc ease in he appea ance o some pa hological diseases such as
Pa kinson’s, ela ed o he concen a ion o a ious neu o ansmi e s in di e en a eas o
he cen al ne ous sys em.
I
he s a e o malnu i ion a ec s he neu o ansmi e con en
i could mean an enhancemen o he
isk
o his kind o disease.
The low-p o ein die supplemen ed wi h all essen ial amino acids me all he
ecommended nu i ional equi emen s (Na ional Academy
o
Sciences, 1978)
;
his is
con i med by he low le el o e ec ound on he concen a ions o he biogenic amines in
bo h egions s udied. Howe e , cau ion mus be exe cised because some di e ences
be ween
CD
and LPD we e de ec ed These include a s a is ical inc ease in he concen a ion
o TYR in bo h egions, and o 5-HIAA in he subs an ia nig a. O he changes, al hough
no s a is ically signi ican , we e hose ound o 5-HT in bo h egions, wi h an inc ease in
one and a dec ease in he o he . O he changes ound, only ha o TYR appea ed o be
ela ed o he low die a y p o ein con en , since simila e ec s we e ound in he wo egions
s udied which was con a y
o
he changes seen in he se o onine gic sys em. Wi h he
a ailable in o ma ion
i
is di icul
o
explain he di e ences in TYR concen a ion be ween
CD and LPD. Taking in o accoun ha phenylalanine does no ac as a p ecu so o TYR
in he cen al ne ous sys em ( he e
is
no phenylalanine hyd oxylase
(EC
1.14.16.1)
ac i i y in he b ain), he inc ease seen in TYR wi h LPD could be ela ed o a majo e lux
o
TYR o he b ain ia he la ge neu al amino acid anspo sys em. Fo his o occu ,
ni ogen om essen ial amino acids would be necessa y
o
syn hesize non-essen ial amino
acids, including TYR, o i is possible ha phenylalanine is con e ed enzymically o
y osine by phenylalanine hyd oxylase, in pe iphe al issues, o bo h. The la e possibili y
seems o be plausible because
o
he simila i y in he phenylalanine con en in CD and LPD
(see Table
I).
E ec
o
sonie essen id amino mid de$ciencies in
he
se o onine gic sys em
Die a y de iciency a ec ed 5-HT me abolism in bo h egions s udied, being mo e ob ious
in he subs an ia nig a. No able was he inc ease in he concen a ion
o
5-HIAA in he
subs an ia nig a. A simila e ec was ound in his s uc u e in isoleucine-de icien a s, and
in ensi ied in leucine, me hionine and phenylalanine de iciencies. Mo eo e , wi h he la e
ea men s he inc ease in 5-HIAA was also accompanied by a signi ican dec ease in he
concen a ion o 5-HT wi h espec o CD and LPD. The di e en egional e ec s on 5-HT
me abolism associa ed wi h he di e en amino acid de iciencies could be due o he
di e en o igins o he 5-HT. The 5-HT in he subs an ia nig a comes p incipally om he
neu onal cell bodies and e minals (Fuxe, 1965; Unge s ed , 1971; Olsen
&
Seige , 1972),
whe eas in he s ia um i comes only om aphe nuclei e minals (Bobillie
e
al.
1976; Van
de Kooi, 1979). The dec ease in 5-HT con en could be due
o
an accele a ion o 5-HT
u no e such as ha desc ibed in se o onine gic ne e e minals inju ed by 5,7-
dihyd oxy yp amine (S achowiak
e
al.
1986). In he la e condi ion he le els o 5-HT
and 5-HIAA we e educed in he hippocampus and sep um a e he lesion. Howe e , as
he magni ude o his dec ease was much lowe o 5-HIAA con en , he 5-HIAA: 5-HT
a io was inc eased. As 5-HIAA is he majo me aboli e o 5-HT in he b ain, an inc ease
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess
EFFECT OF DIET
IN
NEUROTRANSMITT’ER LEVELS
417
in
he 5-HIAA: 5-HT a io may indica e an accele a ed u no e o 5-HT. This possibili y
is suppo ed by a p e ious epo ha o ma ion o
5-[’H]HIAA
om [3H]TRP in he
medulla and spinal co d inc eased a e 5,7-dihyd oxy yp amine adminis a ion (Ge son
&
Baldessa ini, 1974). In he p esen s udy a simila e ec was also ound in he s ia um
when he e was a leucine o aline de iciency. These indings sugges ha in a s ed on LPD
b ain p o ec ion dec eases somewha , especially in he subs an ia nig a. The lack
o
p o ec ion was mo e signi ican when he e was a de iciency in leucine, nie hionine o
phenylalanine. These indings a e simila o hose ob ained by inducing di e en kinds o
damage (Ge son
&
Baldessa ini, 1974; S achowiak e
a/.
1986). I we ela e he magni ude
o he damage o he inc ease in he 5-HTAA
:
5-HT a io, i is highes wi h he me hionine-
de icien die . This ac may be ela ed o he ole o me hionine, since his is a sulphu -
con aining essen ial amino acid which is in ol ed in he syn hesis o cys eine. Cys eine is
a
undamen al componen
o
he pep ide glu a hione. This pep ide cons i u es he majo
non-p o ein sulphu a ed componen
o
all o ganisms and is in ol ed in se e al impo an
p ocesses including de oxi ica ion (Sies e
al.
1983) and he oxida i e me abolism o cen al
ca echolamines (Ho he sall
e
ul.
1982). Thus, glu a hione is undamen al in main aining
he cellula edox s a e (Reed e
al.
1983). A de ici
o
me hionine p oduces a ma ked
dec ease in hepa ic glu a hione concen a ion and should a ec b ain glu a hione
concen a ion, al hough o
a
lesse ex en . This e ec may also be he esul o a dec ease
in p o ec ion agains oxida i e damage as has been epo ed in a i amin E-de icien die
(A. Cas aEo,
J.
Cano
&
A. Machado, unpublished esul s). This may be impo an since
li le is known abou he mechanisms behind he degene a i e p ocess leading, o example.
o Pa kinson’s disease, bu
i
has been sugges ed ha oxic species e ol ed om he
ca abolism o ca echols may be in ol ed in he pa hogenesis (Cohen,
1983;
Fo ns ed
e
al.
1990).
A
de ici o yp ophan a ec ed 5-HT me abolism in bo h egions s udied (5-HT and i s
me aboli e 5-HIAA dec eased). Since 5-HT in he b ain is syn hesized om he essen ial
amino acid TRP, hese esul s a e in acco dance wi h he ac ha he a e o 5-HT
syn hesis in he b ain depends on he a ailabili y o his p ecu so (Fe ns om
&
Wu man,
1971
;
Ca lsson
&
Lindq is , 1978). Nume ous expe imen s ha e demons a ed ha an
inc ease
in
b ain TRP no only inc eases he a e o 5-HT syn hesis bu also inc eases he
whole-b ain concen a ion
o
5-HIAA (Fe ns om
&
Wu man, 1971). Thus, a dec ease in
TRP concen a ion may be expec ed o p oduce a dec ease in 5-HIAA. This inding may
be impo an since, in some illnesses such as oxici y, TRP is adminis e ed as a sca enge
(Gomez-Reino
e
a .
1983) wi hou knowing he e ec o his ea men on he ee plasma
TRP and subsequen TRP and 5-HT concen a ions in he b ain. Besides, li le is known
abou whe he adicals can oxidize TRP and how his would a ec
5-HT
concen a ion.
Howe e , om he amino acid composi ion
o
CD and LPD (9.9 g TRP
in
CD and 2.9
g
in
LPD), only a la ge educ ion in he TRP con en o he die (i.e.
0.3
g TRP in he TRP-
de icien die ) may lead o a deple ion o he TRP pool in he b ain.
The e ec s o he aline-de icien die we e unusual. In he subs an ia nig a he e ec on
he se o onine gic sys em was simila o ha ound wi h o he amino acid de iciencies,
being he e e se o ha in he s ia um (5-HT concen a ion dec eased
in
he subs an ia
nig a and inc eased in he s ia um).
E ec o some essen ial amino
acid
d@iencies
in
he dopamine gic sys em
When he ca echolamine le els we e s udied he e was a no able inc ease in TYR
concen a ion a e he adminis a ion o each o he p o ein-de icien die s in bo h egions
s udied. This e ec was p oduced by LPD and i was main ained in all amino acid
de iciencies s udied wi h he excep ion
o
he phenylalanine-de icien die . The maximum
h ps://doi.o g/10.1079/BJN19920098 Published online by Camb idge Uni e si y P ess