AGE-RELATED CHANGES IN THE RAT BRAIN UNDER ENVIRONMENTAL STRESS DISSERTATION SUBMITTED FOR THE DEGREE OF iHa^ter of ^titlosiapli;^ IN ZOOLOGY ASiss ACHX^A GUPTJL INTERDISCIPLINARY BRAIN RESEARCH CENTER AND DEPARTMENT OF ZOOLOGY ALIGARH MUSLIM UNIVERSITY ALIGARH (INDIA) 1987
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AGE-RELATED CHANGES IN THE RAT BRAIN UNDER ENVIRONMENTAL STRESS
DISSERTATION SUBMITTED FOR THE DEGREE OF
iHa^ter of ^titlosiapli;^ IN
ZOOLOGY
ASiss ACHX^A GUPTJL
INTERDISCIPLINARY BRAIN RESEARCH CENTER AND
DEPARTMENT OF ZOOLOGY ALIGARH MUSLIM UNIVERSITY
ALIGARH (INDIA) 1 9 8 7
: ^ \ ;sr^j*.^."-'»!^
L OS/3 7 ^ ^ **^ •: , i . • » V ' .
DS1394
C B R T I F I C A T E
This i s to cert i fy that Mies Achla Gupta has completed
her research work under our supervision. The dissertation
ent i t led "Age-related changes in rat brain under environmen
t a l stress**, i s an origincJ. contribution and d i s t inc t addition
to the ex i s t ing knowledge on the subject . Sha i s allowed to
submit the work for the degree of Master of Philosophy in
Zoology under Interdiscipl inary Research of the Aligarh MusliBi
University, Aligarh.
(Prof. Dr. A,.-ffrSIDDIQUl) Ph.D.
Chairman Department of Zoology, Allgaih Muslim University, Aligeurh.
(Prof. Dr. MAHDI HASAH) M.S. (Hons), Ph.D., D.Sc, Director Interdisciplinary Brain
Researeh Centre, J.H. MediceJ. College, Aligarh Muslim University, kllgaTh.,
ACKH0VTJSDGEMENT3
No young s c h o l a r , h o w s o e v e r , keen i n p u r s u i t of kjaowledi-';e
and i o a r n i a g can o v e r a c h i e v e much u n l u B s l,ht; ;,';ui(3iaioe of a
s e a s o n e d s c h o l a r who h a s d e d i c a t e d h i s l i f e i n p u r s u i t of
imowledge t h r o u g h h a r d work , t o i l and n e v e r - e n d i n g r e s e a r c h ,
. i s a v a i l a b l e . I t i s i n d e e d my exrtreme good l u c k t h a t P r o f .
D r . Mahdi l l a a a n , D l r o c L o r , 1 u tor-dliic l | ) l i i j a fy Bi ' a in Ri-tiearch
C e n t r e , J . N . M e d i c a l C o l l e g e , A.M,.U., A l i g a r h , a c c e p t e d me a s
h i s d i s c i p l e and \ i n s t i n t i n g l y gave me a l l g u i d a n c e and a s s i s
t a n c e needed a t each s t a g e of my s t u d i e s . I h a v e no words t o
e x p r e s s my g r a t i t u d e t o him f o r a l l t h a t he h a s done f o r me.
I owe s p e c i a l g r a t i t u d e t o ray s u p e r v i s o r P r o f , ^icher
H u u a i a 3 i d ( l l q u i , ChnLrttiari, Du[)artni(>nt of Zoo logy , whose know-
l e d g o mid e x j i e r i e n c e i n r e s u a r c h waH a / / r e a t ai;;;et to mf- la
p u r s u i n g t h i s work .
I s h a l l n e v e r f o r g e t D r . S . Badi*ul Hasan and Mr. Ai'.i2
Khan, R e a d e r s i n t h e D e p a r t m e n t of Community M e d i c i n e , v/ho
e n c o u r a g e d and a s s i s t e d me i n ray scheme of r e s e a r c h v/ork and
s t a t l f j t l o a l work, ror.[)f;o t i vc I y .
D r . F a k h r u l I s l a m , L.-. S . Saleem H a i d e r and D r . ( M r s . )
Tayyaba Q a d r i r e n d e r e d g r e a t a s s iL^ tance and gave v a l u a b l e
s u g g e s t i o n s aiid g e n e r o u s h e l p i n t h e p r e p a r a t i o n of my r e
s e a r c h v/ork. I do n o t vnsh t o m i s s t h e o p p o r t u n i t y of c o n v e y -
ii
ing my sincere thanks to them.
I owe special thanks to Miss Prlti Vadhava and Mr. Naseem
Ahmad Khan for their cooperation, assistance and encouragement
in the preparation of this manuscript. Thanks are also due to
Dr. Yagana Bano and Mr. Masood Zaheer Naqvi for their help and
cooperation. I cannot forget to make special thankful mention
of Mrs. Amita Gupta, a research scholar in Biochemistry Deptt.
for her cooperation and assistance.
I am dutihouTid to thankfully mention the names of Mr.
Syed Mohammad o id Dr. (Mrs.) Madhu Chovdhary, artists in the
Department of Anatomy and Community Medicine, respectively,
who helped me a lot in the preparation of my figures and
charts included in my dissertation.
I shall fail in my moral obligation if do not thank
Mr. Auhfaq Ahmad, Deptt. of Applied Mathematics, Z.H. College
of Engineering and Technology for his help in calculating the
ANOVA and Mr. Syed Mujeer, Mr. Mansoor Ahmad and Mr. Wajid
Husain, Central Photography imd Audio-visual Section for
photop:raphs for my dissertation.
I am also thankful to all the members of the Laboratory
staff of the Anatomy Department, specially to Mr. Shaukat Ali
for their cooperative attitude.
I believe that the affectionate blessings, spoauaneous
Ill
and unstiated cooperation of my TAUJEE, Mr. S. P. Gupta and
my father, Mr. S. C. Gupta have borne fruits and enabled me
to bring out this small piece of research work. A special
word of thanks is also due to my younger brother, Mr. A. K.
Gupta, who helped me in my statistical calculations.
' Last but not the least I owe special gratitude to my
respected mother who gave me ample free time to pursue my
study and research work at the cost of her comfort. I cannot
forget my younger sister, Miss Archana Gupta who always ea~
couraged me through her letters.
Finally, the financial assistance from Indian Council
of Medical Research, New Delhi, in the form of Jiuiior n..nu?afch
Fellowship, is thankfully acknowledged.
ACHLA GUPTA
ABSTRACT
A l t e r a t i o n s i n l i p i d p r o f i l e s and i n t h e r r ; t e of li/.i'l
p e r o x i d a t i o n were s t u d i e d i n t h e d i f f e r e n t r e g i o n s of ON 3
of a g i n g r a t s f o l l o w i n g r e s t r a i n t s t r e s s f o r 24 h o u r s . In
t h e 6 months o l d r a t s , t h e c o n c e n t r a t i o n of t o t a l l i p i d s ,
c h o l e s t e r o l and p h o s p h o l i p i d s were i n c r e a s e d i n v a r i o u s
r e g i o n s of b r a i n but d e c r e a s e d i n t h e s p i n a l c o r d , Flowever,
t h e c o n t e n t s of g a n g l i o s i d e s and t h e r a t e o f l i p i d p e r o x i
d a t i o n were d e c r e a s e d i n c e r e b r u m , c e r e b e l l u m ajid b r a i n ster;.
a f t e r 24 h o u r s r e s t r a i n t s t r e s s . On t h e o t h e r h a n d , i n 12
months o l d r a t s t h e l e v e l s of t o t a l l i p i d s , c h o l e s t e r o l ai.d
g a n g l i o s i d e s were d e p l e t e d i n v a r i o u s r e g i o n s of CHS, excei: t
c e r e b e l l u m . I n t e r e s t i n g l y , t h e c o n t e n t of p h o s p h o l i p i d t:
were d e c r e a s e d i n a l l t h e r e g i o n s of CNS and t h e r a t e *'
l i p i d p e r o x i d a t i o n was i n c r e a s e d i n a l l t h e r e g i o n s of C ]:< S
a f t e r r e s t r : a n t s t i - e s s f o r ' 4 h o u r s . R e g i o n a l h e t oro,»-" :'!.C'' ;
was a p p a r e n t :.ot o n l y i n t h e c o n c e n t r a t i o n of l i o l d c : - :
l i p i d p e r o x i d a t i o n in t h e v a r i c j u s r>;,iTiiS ):' tr^' •.• . •
but a l s o f 'A i^ovi t.i:: r e : - t r a i n t s t r e s s .
LIST OP FIQURBS
Figure No. Page
1. Correlation between scientific developments, stress and its effect on aging
2. General adaptation syndrome (O-AS)
3. Various concepts of stress
4. Restraint cage lodging an albino rat, immobilized for 24 hours
5. Photograph showing dorsal view of the rat brain
6. Dissection of rat brain parts for biochemical studies
7. Calibration curve for the estimation of total lipids
8. Calibration curve for the estimation of phosphorus
9. Calibration curve for the estimation of cholesterol
10. Calibration curve for the estimation of gangliosides
11. (a) Control animal
(b) Effect of restraint stress on the animal
12. Gastric mucosal stxrface of rat stomach
(a) In control animals
(b) In stressed ones, multiple ulcers (arrow)
2
6
7
25
27
28
50
34
37
39
44
44
45
45
LIST o r TABLB3
Table No. ^ ^ e
1. Rest ra in t s t ress - induced changes in the l eve l s of t o t a l l i p i d s in d i f fe ren t bra in regions of 6 months old r a t s — 46
2. Res t ra in t s t ress - induced changes in the l e v e l s of t o t a l l i p i d s in d i f fe ren t brain regions of 12 months old r a t s — 47
3. Restraint stress-induced changes in the levels of phospholipids in different brain regions of 6 months old rats ... 49
4. Res t ra in t s t ress - induced changes in the l eve l s of phospholipids in d i f fe ren t bra in regions of 12 months old r a t s . . . 50
5. Res t ra in t s t ress - induced changes in the l eve l s of c h o l e s t e r o l in d i f fe ren t bra in regions of 6 months old r a t s . . . 51
6. Res t ra in t s t ress - induced changes in the l e v e l s of c h o l e s t e r o l in d i f f e ren t b ra in regions of 12 months old r a t s . . . 52
7. Res t ra in t s t ress - induced changes in the l e v e l s of gangl ios ides in d i f f e ren t b ra in reg ions of 6 months old r a t s . . . 53
8. Res t ra in t s t r ess - induced changes in the l e v e l s of gang l ios ides in d i f fe ren t b ra in regions of 12 months old r a t s . . . 54
9. Res t ra in t s t r ess - induced changes in the r a t e of l i p i d peroxidat ion in d i f fe ren t b ra in reg ions of 6 months old r a t s . . . 56
LIST or TABLES (continued)
Table No. Page
10. R e s t r a i n t s t r e s s - i n d u c e d changes in t h e r a t e of l i p i d p e r o x i d a t i o n i n d i f f e r e n t b r a i n r e g i o n s of 12 months old r a t s . . . 57
1 1 . Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of totsuL l i p i d s f o l l o w i n g 24 hoxirs r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 6 months o ld r a t b r a i n and s p i n a l cord . . . 59
12. Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of t o t a l l i p i d s f o l l o w ing 24 hours r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 12 months o ld r a t b r a i n and s p i n a l cord . . . 60
13 . Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of p h o s p h o l i p i d s f o l l o w ing 24 hours r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 6 months old r a t b r a i n and s p i n a l cord . . . 61
14. Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of p h o s p h o l i p i d s f o l l o w i n g 24 hou r s r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 12 months old r a t b r a i n and s p i n a l cord . . . 62
15. Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of c h o l e s t e r o l f o l l o w i n g 24 hours r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 6 months o ld r a t b r a i n and s p i n a l cord . . . 63
16. Trend of a n a l y s i s of v a r i a n c e (ANOVA) on t h e l e v e l s of c h o l e s t e r o l f o l l o w i n g 24 hour s r e s t r a i n t s t r e s s i n d i f f e r e n t r e g i o n s of t h e 12 months o ld r a t b r a i n and s p i n a l cord . . . 64
LIST OF TABLBS (continued)
Table No. Page
17. Trend of analysis of variance (AHOVA) on the levels of gangliosidee following 24 hours restraint stress in different regions of the 6 months old rat brain and spinal cord ... 65
18. Trend of analysis of variance (ANOVA) on the levels of gangliosides following 24 hours restraint stress in different regions of the 12 months old rat brain and spinal cord ... 66
19. Trend of analysis of variance (ANOVA) on the levels of rate of lipid peroxidation following 24 hours restraint stress in different regions of the 6 months old rat brain and spinal cord^ ... 67
20. Trend of analysis of variance (ANOVA) on the levels of rate of lipid peroxidation following 24 hours restraint stress in different regions of the 12 months old rat brain and spinal cord ... 68
C 0 M T B H T 8
ACKUOWLEDGEl NTS
ABSTRACT
LIST OF FIGURES
LIST OF TABLES
Page
I . INTRODUCTION
1.1 Ageing
1.2 S t r e s s
1.5 R e s t r a i n t s t r e s s
1.4 R e s t r a i n t or Immo"bili2iation used a s s t r e s s o r
1.5 Lipids
1.6 Lipid peroxidation
1.7 Aims and Objectives
II. MATERIALS AND METHODS
2.1 Animals
2.2 R e s t r a i n t s t r e s s
2 .3 D i s s e c t i o n and i s o l a t i o n of d i f f e r e n t p a r t s of "brain
2 .4 E x t r a c t i o n of l i p i d s from b r a i n
2 .5 E s t i m a t i o n of t o t a l l i p i d s
2 .6 E s t i m a t i o n of phospha te
2.7 E s t i m a t i o n of c h o l e s t e r o l
2 .8 E s t i m a t i o n of g a n g l i o s i d e s
1
3
4
8
9
14
20
22
24
24
24
24
26
29
31
35
38
Page
2.9 Determination of rate of lipid peroxidation
2.10 S t a t i s t i c a l analysis
2.11 Ana lys i s of v a r i a n c e (ANOVA)
40
42
42
I I I . RESULTS
3.1 Physical signs
3.2 Effect of r e s t r a in t s t r e s s on regional brain l ip id levels in aged ra te
3.3 Effect of restrednt s t ress on the ra te of l ip id peroxidation
3.4 Analysis of variance
43
43
43
55
58
17, DISCUSSION
BIBLIOGRAPHY
LIST OF PUBLICATION AND PRESENTATIONS
69
76
91
INTRODUCTION
I. INTRODUCTION
God created living beings but made them mortal. Thus
birth presupposes death. In between birth and death are
various stages of life, viz., infancy, childhood, youth and
old age. This gradual process from birth till natural death
is called ageing. Ageing involves sloir and gradual change
both in physical appearance and in the various regions of
the brain. The latter is the product of several factors,
both internal and external. The advancement of modem
sciences ushered in an era entirely unkno\m to our fore
fathers. Thus began the industrial revolution. Mass pro
duction of things started. Manual labour became uneconomical
and was replaced by machinery. In this process many lost
their source of livelihood. Some of them migrated to the
centres of industrial and commercial activities. This led
to urbanization which posed problems of its own. Carefree
life received a rude shock. Stress and strain of every day
life posed a big threat to the peace and tranquility hitherto
enjoyed by man. This has since engaged the attention of
scientists who have accepted the challenge to study carefully
and analytically the whole problem confronting the mankind.
Medical scientists contributed a lot in the advancement of
medical science whereby life span increased but the impact of
stress on hvunan life, especially due to industrialization and
INCREASE IN THE POPULATION OF THE AGED.
Problems?
G E R O N T O L Q ^
LIFE-EXPECTANCY increased
I ADVANCEMENT
IN VMedicalSciences 2.Science and
Technology
INDUSTRIALIZATION AND
URBANIZATION
R ^ . l CORRELATION BETWEEN SCIENTIFIC DEVALOPMENTS,STRESS AND ITS EFFECT ON AGING.
urbanization, has created problems for them which require
deep study in the field of age-related changes in the various
regions of brain due to environmental stress (Fig. 1).
1.1 AGEIMG
Ageing is a universal and inevitable scientific and
social challenge confronting hiamanity. The lives of all
multicellular organisms begin with conception, extend through
development, maturity, senescence and end in death. Accord
ing to G. H. Hunt (1959), "the term ageing process, as
applied to living organisms, is the genetically determined
progressive and essentially irreversible diminution with the
passage of time of the ability of an organism or of one of
its parts to adapt to its environment, manifested as dimi
nution of its capacity to withstand the stresses to which it
is subjected, and culminating in the death of the organism".
Comfort (19 5^ said that ageing is an increased liability to
die or an increasing chronological age or the passage of the
life cycle. Ageing processes have been defined by Ma3mard
Smith (1959) as those which render individuals more suscep
tible, as they grow older, to the vsurious factors, intrinsic
or extrinsic, which may cause death.
Recently, Backmann and coworkers (1984) are of the view
that ageing is a differentiation process which is caused by
a phase-specific genetic information and by changes during
the processing of the primary transcript to the functional
mRNA. These changes influence the functional accuracy of
enzyme systems vhich are involved in gene realization. This
means that with ageing of an individual the error load
increases steadily to reach a threshold value. This causes
a collapse of the dynamic and thermodynamically controlled
interplay of the metabolic events.
1.2 STRESS
The literal meaning of the word 'stress' is 'condition
causing hardship'. In the language of life science, the
meaning of 'stress' is "an intense force, strain, agent or
mentaJ. condition which produces a defense reaction, which if
continued or intensified may lead to pathological lesions".
In other words, stress denotes the 'rate of wear and tear in
the body*. According to Selye (1956), stress is the nonspeci
fic response of the organism to any demand made upon it but
this definition would not be satisfactory any more, because
it is so wide that any physiological response and any exter
nal stimulus could be brought under this concept. Stress is
a very divergent phenomenon. It was generally felt that there
is a natural tendency to speak of a stress situation only when
the demand exceeds a certain level and is experienced as un
desirable or unacceptable. In the opinion of Tuwiler (1971),
'stress' like the word love, is broadly understood but poorly
defined. He considered the life as a series of micro- and
macro-adaptations to a constantly changing internal and exter
nal environment; and emphasized that s tress was an everpresent
condition. Rabkin and Struening (1976) mentioned that s tress
l ike anxiety, was a broad and general concept describing
organisms' reactions to environmental demands, Selye (1979)
further emphasized that s tress causes certain changes in the
structure and chemical composition of the body. Some of
these changes are merely signs of damage, others are manifes
tat ion of the body's adaptive reactions, i t s mechanism of
defense against s t re s s . The t o t a l i t y of these changes, the
s tress syndrome, i s called the general adaptation syndrome
( G . A . S . ) which develops in three stages, (1) the alarm reac
t ion , (2) the stage of res istance, and (3) the stage of
exhaustion (Fig. 2 ) .
Stress has different concepts in different branches of
science (Pig. 3 ) . Any environmental factor that can s i g n i f i
cantly modify an animal's b io log ica l responses result ing into
s tress i s cal led a s tressor .
Rabkin and Struening (1976) remarked that "social
stressor* refers to personal l i f e changes, such as bereave
ment, marriage, or l o s s of job, which a l ter the individual 's
socisJ. s e t t ing . A more speci f ic def in i t ion was proposed by
Holmes and Rahe (1967) who defined as soc ia l s tressors , any
set of circumstances the advent of which s i g n i f i e s a required
change in the individual 's on-going l i f e pattern.
{iiija (S - E)
(ii) (S - A)
(Ui)b {S - E)
Fig.2 GENERAL ADAPTATION SYNDROME (G.A.S.)
PHYSICAL • LOAD • PRESSURE .•TEMPERATURE
BIOCHEMICAL • METABOLIC
CHANGES • ENZYMES • HORMONES.
PSYCHOLOGICAL • DEPRESSION (STRESS
GUILT FRUSTRATlOt
PHYSIOLOGICAL • BEHAVIOUR • SITTING
YAWNING
SOCIOLOGICAL BEREAVEMENT MARRIAGE
^ LOSS OF JOB
MEDICAL • RATE OF
WEAR AND TEAR
Fig.3 VARIOUS CONCEPTS OF STRESS
8
Stress plays a role in such diverse maaifestations of
l i f e as ageing, the development of indiv idual i ty , the need
for s e l f expression, and the formulation of man's ultimate
aims. Psychological s tress ar ises in man due to the effect
of various factors on the neocortex. Experiments in animals
have shown that deep and prolonged psychosomatic disturbances
arise from psychological s t re s s .
Environmental s tress invokes compensatory metabolic
changes through modification of the quality and quantity of
enzymes that are normally rate- l imit ing or under fine con
t r o l or inducible by hormones (Ramasarma, 1978). The pro
cesses of adaptation at the ce l lu lar l e v e l to chronic s tress
seem to occur by sequential changes in hormones, enzymes and
metabolites leading to anew steady-state . Ramasarma (1960)
emphasized that those changes which are benef ic ia l to the
organism's need are promoted and accelerated. On long expo
sure, the changed pattern (due to stress) s e t t l e s to a stage
representing the de l icate balance of ce l lular constituents
best suited to the metabolic demands of the organism.
1.5 RESTRAINT STRESS
When an animal is kept under control in such a way that
it cannot move its body at its will it is said to be under
restraint stress. For example, when a rat is kept in a mini-
cage with the result that its movement is restricted, it is
said to be under restraint stress.
In the works of Renaud (1959), Baker et al., (1962),
GaniB (1962), Thompeon (1966), and Girardet (1974) details
of many types of restraint devices, cages and other appara
tus for rats, which are commercially available for general
or specific needs, may be seen.
1.4 RESTRAINT OR IMMOBILIZATIOM USED A3 A STRESSOR
Restraint or immobilization is one of the commonly used
laboratory stressors which has the apparent advanteige of be
ing relatively simple. It was further observed that this
particular stressor is compounded of fear, isometric muscular
activity, and muscle cramps due to specific positioning.
According to Tuwiler (1971), immobilization poses some prob
lems since the magnitude of the stressor varies with exper
ience and, more subtly, with differences in positioning and
handling the animals between experiments and experimeutors.
Seegal (1981) advocated that immobilization is usually
selected as a stressor or as a means of inducing stress
because of its being simple and also due to the large n\imber
of stuaies that have employed this stressor (Du Ruisseau et
al., 1979; Kawakami et al., 1979; Kobayashi et al., 1976;
Reigle and Meites, 1976; Kventnansky and MikulaJ, 1970;
Krigger et al., 1979; and Zholkute and Udupa, 1978, 1979).
After chronic restraint (continuous restraint for 24 to
48 hours) involution of the thymus and adrenal, hypertrophy
10
was reported by Selye (1936). Chronic restraint, of course,
is also complicated by concomitant voluntary or involuntary
fasting, which varies both with accessibility of food and
with the emotional state of the animal. Therefore, in experi
ments using immobilization as a stressor, the control (un
stressed) animals should also be kept deprived of any food
for the same period as the immobilized ones.
The production of gastric ulcers after chronic immobili
zation was noticed by Rossi et al., (1956). Brodie and Hanson
(i960) observed that the degree of ulceration and ulcer loca
tion varies species to species. They reported that mice and
rats show a high ulcer incidence, guinea pigs have a lower
incidence, and hamsters a very low incidence of ulceration.
They further noted that rabbits and monkeys ordinarily have
little or no ulceration upon restraint. Parisio and Clementi
(1976) noted stress-induced ulceration in gastric mucosa in
albino rats.
Liberson et al., (1964) detected a decrease in serotonin
in cerebral cortex and hippocampus after forced positioning
of animals without direct physical restraint other than conti
nually replacing the animal in position. An increase in the
serotonin concentration after long and short intervals of
immobilization was observed by De Schaepdryver et al., (1969).
Bliss and Zwanziger (1966) noted that restraint resulted in a
slight increase in the levels of GABA (gamma amino butyric acid)
11
An increase in tyrosine amino-transferase activity due
to chronic immobilization was observed by Hanninen and Har-
tiala (1967). They noted that this increase is dependent
upon the adrenals and only occurs in animals showing develop
ment of ulcers. These workers also reported increased
tryptophan oxygenase activity two-fold by 6 hours of restraint
which was somewhat more after 24 hours.
Welch and Welch (1968) detected an increase in brain
norepinephrine levels in mice, housed singly in isolation
cages after short restraint (7 minutes). Bliss and Zwanziger
(1966), Corrodi et al., (1968), on the other hand, noted 10
to 20 per cent decrease in brain norepinephrine levels of
mice, guinea pigs, or rats restrained for two or more hours.
According to Bliss and Zwanziger (1966), these changes were
most marked in cerebellum and hypothalamic areas. A histo-
chemical depletion of central noradrenergic neurons after two
or more hours of immobilization was noted by Corrodi et al.,
(1968).
In acute experiments with this stressor, plasma (De
Schaeperyver et al., 1968) and adrenal (Zimmerman and Critchlow,
1967) corticoids are elevated, and in contrast to stressors
such as hunger or shock, some degree of adaptation to exper
ience occurs after immobilization stress.
Kvetnansky and Mikulaj (1970) reported a decrease of adre
nal catecholamine content and a marked elevation of urinary
1?
catecholamine excretion after forced immobilization, as well
as many other stresses. Interestingly, increased dopamine
levels were observed after acute restraint by Welch and Welch
(1968), while chronic restraint led to their fall l>De Schaep-
dryver et al., 1969).
Rudeen and Morgan (1975) showed that immobilization
stress affected the serotoninergic system differently in
five areas (cerebral cortex, brain stem, diencephalon, hippo-
campal formation, and corpus striatum) of the brain in rats
which were immobilized for the time intervals of 30, 60, 120,
180 and 300 minutes. They suggested that the decrease in the
elevation of brain 5-hydroxyindoleacetic acid (5-HIAA) with
continued stress might reflect physical exhaustion or adap
tation to the stress or might indicate an increase in the
excretion of 5-HlAA from the brain.
Kvetnansky et al., V1978) implicated hypothalamic cate
cholamines in neuroendocrine processes; as evidenced by dec
rease in the catecholamine contents of specific nuclei and
areas of the rat hypothalamus. They suggested that adrenaline-
forming neurons in the anterior hypothalamic region were
involved in the complex central regulatory pathways for the
integration of tne peripheral adrenergic responses.
Furthermore, immobilization stress was found to be
associated with significant increase in plasma ACTH and corti-
1'
coeteroid concentrations and decrease in anterior pituitary
ACTH concentration (Krigger et al., 1979). These workers
observed no significant change in medial basal hypothalamic
or median eminence ACTH concentrations and suggested the
involvement of different systems in the origin and regulation
of brain and pituitary ACTH. Selye (1976) stated that the
inhibitory effect of stress on plasma testosterone levels was
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LIST OF PUBLICATION AND PRBSENTATIONS
PUBLICATION
1. Gupta A and Haeaa M. A g e - r e l a t e d changes i n l i p i d p r o f i l e s and l i p i d p e r o x i d a t i o n in t h e GNS fo l lowing r e s t r a i n t s t r e s s . Ind J Med Res . ( i n P r e s s ) .
PRESENTATIONS
1. Grupta A and Hasaa M. R e s t r a i n t s t r e s s - i m d u c e d a l t e r a t i o n s
i n CHS l i p i d p r o f i l e s of t h e ag ing r a t s . P r e s e n t e d a t
Thi rd N a t i o n a l Conference on Aging, -vrith a s p e c i a l s e s s i o n
on B r a i n Aging, he ld a t School of L i f e S c i e n c e s , U n i v e r
s i t y of Hyderabad, Hyderabad on Nov. 26 -28 , 1986.
2 . Gupta A, Hasan M and Haider S S. A l t e r a t i o n s i n l i p i d
p r o f i l e s and l i p i d p e r o x i d a t i o n i n v a r i o u s r e g i o n s of t h e
b r a i n of aging r a t s fo l l owing r e s t r a i n t s t r e s s . P r e s e n t e d
a t XXIV N a t i o n a l Conference of Anatomical Soc ie ty of I n d i a
he ld a t J . N . Medica l C o l l e g e , A.M.U., A l i g a r h on Dec.
28-50 , 1986.
5 . Hasan M, Gupta A and Chandra S V. Trace e lements in d i s
c r e t e r e g i o n s of t h e r a t CNS: Age r e l a t e d and r e s t r a i n t
s t r e s s - i n d u c e d changes . P r e s e n t e d a t I n t e r n a t i o n a l sympo
sium on Metabolism of m i n e r a l s and t r a c e e lements i n human
d i s e a s e s h e l d a t A l i g a r h , New D e l h i and S r i Nagar (Kashmir)
from 18 t o 30 S e p t . , 1987.
4 . Hasan M, Gupta A and Chandra S V. S i g n i f i c a n t a g e - r e l a t e d
e l e v a t i o n of aluminium i n d i s c r e t e r e g i o n s of t h e r a t CHS:
D e p l e t i o n by r e s t r a i n t s t r e s s . P r e s e n t e d a t t he 36 th
N a t i o n a l Conference of Anatomical S o c i e t y of I n d i a he ld on
28-30 D e c , 1987 a t P t . J.N.M. Medica l CoUege , Ra ipu r .