In order to study the effects of hypokinesia and circadian rhythm restructuring on the morphological and functional status of the hypothalamo-hypophysic-adrenal system, young male Wistar rats were placed in small cages for varying periods. The animals were decapitated and preparations were made from sections of the brain and adrenals and numerous destructive changes were noted in the investigated regions of the brain, indicating that the condition of these areas is directly affected by disruption of established rhythms in physiological processes

Razin, S. N.

Rychko, A. V.

English

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NASA TECHNICAL MEMORANDUM
	
NASA TM-76051
STATE OF THE BODY IN DISORDERS OF DIURNAL
PHYSIOLOGICAL RHYTHMS AND LONG-TERM HYPOKINESIA
S.N. Razin and A.V. Rychko
Translation of "Sostoyaniye organizma pri narushenii
sutochnykh fiziologicheskikh ritmov i dlitel'noy
gipokinezii," Vrac.hebnoye delo, No. 5, 1976,pp. 104-106
(NASA-TIN-76051) STATE GF 28E BODY IN
	 W60-22969DISORDERS OF DIURNAL PBTSIOLOGICAL E8TTERS
AND LONG-TEEE BTPORIIESIA (National
Aeronautics and Space Ad ministration) 7 p
	 Doclas8C 102/NF A01
	 CSCL 06S G5/52 46888
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NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546 	 MARCH 1980
JJMDUL-1014 RESTRICTIONS OVERRIDDEN
wsr, gr;iwntiXi,cati cL Tec'rIA.':a1 Itiformat ion Facility
1	 R^por N,. — _ - -- - - --
TM-76 051
2.	 Government Accession No. 3.	 Recipient's Catalog No.
d. Title and Subtitle
	 STATE OF THE BODY	 IN	 DIS —
ORDERS OF'DIURNAL PHYSIOLOGICAL
S.	 Report Date
March 1980
6.	 Performing Organization CodeRHYTHMS AND LONG-TERM HYPOKINESIA
7.	 Author(t) e.	 Performing Organization Report No.
S.N. Razin and A.V.	 Rychko
Department of General Anatomy, 10.	 work unit No.
Vinnitsa Medical Institute
11.	 Contract or Grant No.
NASW- 1 99.	 Performing Organization Name and Address
Leo Kanner Associates
Redwood City, CA 94063
13.	 Type of Report and Period Covered
Translation
12.	 Sponsoring Agency Nome and Address
National Aeronautics and Space Adminis-
tration, Washington DC 20546
14.	 Sponsoring Agency Code
15.	 Supplementary Notes
Translation of "Sostoyaniye organizma pri narushenii
sutochnykh fiziologicheskikh ritmov i dlitel'noy gipokinezii,
Vrachebnoye delo, No.
	 5,	 1976,	 pp.	 104-106.
16.	 Abstract
In order to study the effects of hypokinesia and circad-'_an
rhythm restructuring on the morphological and functional
status of the hypothalamo-hypophysio-adrenal system, young
male Wistar rats were placed in small cages for varying
periods.	 The animals were decapitated and preparations w--re
made from sections of the brain and adrenals.
	 Lipid deposi-
tion and atrophy were found in the adrenals and numerous
destructive changes were noted in the investigated regions
of the brain, indicating that the condition of these areas
is directly affected by disruption of established rhythms
in physiological processes.
17.	 Key words ( Selected byAutAor ( 0) 18. Distribution statement	 This	 copyrighted
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further copying is permitted
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ri&P'I10u 1UG -i IUN ICE TRIC_VIONS OVERRIDDEN
NMA Scit3ntiSia ;end Tcchn.;ca.l Information Facility NASA-HC
STATE OF THE BODY IN DISORDERS OF DIURNAL
PHYSIOLOGICAL RHYTHMS AND LONG-TERM HYPOKINESIA
S.N. Razin and A.V. Rychko
Department of General Anatomy; Vinnitsa Medical Institute
Pathological changes in many of the	 functional systems	 /104*'
may arise during frequent and long-teem disruptions of the diurnal
periodicity of basic physiological processes (A.N. Litsov, 1969,
1971; E. Buning, 1961).
It has been established that prolonged restriction of motor
	 d
activity is accompanied by morphofunctional changes in many organs
and systems of the body. This involves disruptions of the structure
	 #
of the musculoskeletal apparatus (V.V. Portugalov et al., 1971;
3.A, Makarov, 1974; G.D. Rokhlin and E.P. Levitas, 1975), disorders
of the cardiovascular system (M.G. Prives, 1971; B.S. Katkovsky and
Yu.D. Pometov, 1971; O.M. Mikhaylova, 19'1 4), organs of respiration
and elimination (V.S. Baybara, 1971; I.S. Balakhovskiy et al., 1971),
and disorders of the central and peripheral nervous systems (A.Ya.
Tizul et al., 1972; A.A. Panov et al., 1973; V.V. Tkachev and
E.N. Kul'kov, 1975).
The goal of this work was to study the morphofunctional rearrange-
ment of the hypothalamo-hypophysio-adrenal system -- the primary
hormone regulator of the body's involuntary functions -- during
gross disruption of the rhythms in physiological processes in 12
hour (a day), protracted (30, 60, 90 days) restriction of motor
	 /105
activity. Taken into consideration were the reactions of the young,
developing bodies of inbred animals to the influences we have discussed.
Young (2.5 months) male Wistar rata were studied (exclusive of hor-
monal shift recurrence). Fifty animals were studied in all (8 -- the
background group, and 7 animals each in experimental and control
groups for each period of hypokinesia).
The model for hypokinesia that we used was created by placing
the animals in cages for from 7 to 19 hours, acutely restricting
*Numbers in the margin indicate pagination in the foreign text.
1
PNO
tl
.
	 •1
the animals' movements. Experimental animals were kept under usual
vivarium conditions for the remaining time.
At the end of the experiment the rats were decapitated, body
weight was determined, and the brain, hypophysis, and adrenals were
removed. The latter were weighed on a torsion balance. All the data n-C
obtained were worked up using variation statistics.
The hypothalami and hypophyses were fixed in Bouin's fluid and
the adrenals in 10% neutral formalin. Following removal the organs
were covered in paraffin. Content of neurosecretory substances in the
frontal sections (5-7 micrometers) of the hypothalamus in the supra-
optic region, paraventricular nucleus, and hypothalamo-hypophyseal tract
was determined using the Gomori-Gabou method, and the RNA was shown
using Brasch's method. Hypophyseal preparations were stained using the
Helm-Diban method, and the adrenals were stained with hematoxylin-eosin.
In addition, sections from the adrenals obtained using a freezing
microtome were stained with Sudan-III for the determination of lipids.
The obtained data indicate that the body's growth and develop-
ment are arrested when physiological rhythms are grossly disturbed
by artificial hypokinesia. Hence, the weight deficit of the experi-
mental animals relative to the controls amounted to 28.1, 30.6, and
20% after 30, 60, and 90 days of hypokinesia, respectively.
Change in the adrenals was manifested by a sharp increase in
the relative weight of the glands during the first period of
motion restriction and decreasa in these indices in the subsequent
one. They did, however, remain at a higher level relative to the
control group of animals (Fig. 1). Morphological changes in the
adrenals after 30 days of the experiment were manifested by pro-
nounced hypertrophy of the fascicular layer, and a large quantity
of alveolar, vacuolized, and clear cells with spherical and pyk-
notic nuclei in them. A significant quantity of large drop lipids
was observed in this layer, along with a decrease of them (relative
to the controls) in the glomerular layer, and the appearance of
lipid inclusions in the sudanophobic zone. Irregular borders between
layers could be noted here and there. In the subsequent period of
the experiment (60 and 90 days), atrophy of the adrenal cortices
developed, borders between layers disappeared, and massive deposition
2
- _.. -....^..^.r.._._^^_........ ^.....^ -.... ,^. _-,	
_ -_
of large droplets of lipids was
noted in the glomerular and
fascicular zones.
ago
•: ^.
Alterations in the paraven-
a°so
tricular and supraoptic areas of
0.00
m K, r, KS r 7 KJ rJ
the hypothalamus following 3n days
.	 :
°	 m.O.W of hypokinesia were characterized
a K,.K7 •Kj-R wm" 30.6000 cifrW
br,,r,,r,.euwNwmr30.60a9OFrW by a ,zute dilation of the vascular
Fig.	 1.	 Relative weight of network, a large quantity of dark
adrenals in rats during hypo- cells, hypertrophied neurons with
kinesia.
alveolar cytoplasms and degenerative
Key:	 a.	 Control:	 30,	 60,	 and pyknomorphic cells, which were
90 days;
b.	 Hypokinesia:	 30,	 60, sclerosed in places.	 Dilated axons
and 90 days. filled with neurosecretory substance
were observed along the course of the hypothalamo-hypophyseal tract.
The considerable accumulation of neurosecretory substance was present
in the neurohypophysis around dilated sinusoidal capillaries. 	 In the
adenohypophysis there was a considerable decrease (relative to con-
trols) of acidophilic cells and amphophils, and chromophobe secretions
were noted.
I
These data are evidence that the hypothalamo-hypophyseal system 	 1106
is in a state of heightened functional activity, although degenera-
tion of some structural elements and the appearance of heavy neuro-
secretion can already be dis;,inctly observed. In the subsequent
period of the experiment, the majority of the morphofunctional neuro-
secretory elements underwent irreversible destructive changes. The
I	 supraoptic region had a macrocellular neuroglial structure. There
was an insignificant quantity of se:;:? etory neurons. They were of
large size (acutely hypertrophied, with a considerable number of
optically empty vacuoles, which filled the periphery of the neurons)
and contained solitary large Gomori-positive granules, which were
superficially adsorbed. A minor quantity of small neurosecretory
granulations were discovered in the central paraventricular zone.
Nissl bodies, in the form of small porous, pale lumps, were dis-
tributed between the vacuoles and accumulations of pyroninophilic
i
t
3
granulations in the central paraventricular zone. The remaining
cellu'ar structures of the nucleus were in various stages of re-
gression. A part of the cells were determined to be pyknomorphic
(stained only in places and having uneven contours). The other
part was cell remnants -- membrane fragments. Their nuclei did not
appear, and large vacuoles seriously deformed the contours of the
cells. The capillaries were collapsed and neurosecretory substance
did not appear in the dilated axons. In the base of the supraoptic
area, where the hypothalamo-hypophyseal tract forms, small Gomori-
positive granules were detected, and individual foci of large
I
I	
accumulations of neurosecretory substance were encountered here and
(	 there. Scanty content, of small neurosecretory substance granules
was noted around the vessels in the medial eminence. The posterior
4	 lobe of the hypophysis was degraded and had an alveolar structure.
C	 Solitary granules of neurosecretion were detected around the capil-
lary dilatations of the main posterior part of the neurohypophysis.
In its frontal lobe pronounced discomplexation of the trabeculaei
was noted, as was the predominance of chromophobes, the presence
of colloid in the lumens of the gland's cells, and accumulation of
i	 it in the follicles of the intermediate lobe.
These data permit clarification of the dynamics of morpho-
functional changes in the hypothalamo-hypophysio-adrenal system
which bring about integration of tts motor and involuntary functions.
Self-reg -Alation, through homeostatic reactions, is a property of the
hypothalamo-hypophysio-adrenal system, as it is for any functional
system. And since extramotor activity may not occur without cor-
responding shifts in metabclism and self-regulation, it is quite
understandable that gross disruption of the rhythm of physiological
processes, caused by hypokinesia, directly affects the condition
of the cited systems (both in the central nervous system and in
various forms of metabolism).
According to G. Sel'ye (1960), during a prolonged and intensive
influence of stimulation, there first arises the reaction of "alarm,"
characterized by a sharp increase in the hormonal activity of the
4
adrenal cortex, after which there follows a growth in the body's
resistance to the influence of both the given stress factor and
o," other factors qualitatively different from it. The exhaustion
stage then arises, accompanied by a decrease in the body's resis-
tance, which may lead to death. Morphofunctional changes in the
hypothalamo-hypophysio-adrenal system following 30 days of hypo-
kinesia are evidence that this system is in the resistance stag3
and is still capable of returning to its normal functioning state
when the action of the stimulus is withdrawn and the normal rhythm
of the body's physiological proa::sses is restored. Later, following
60 and particularly 90 days of the experiment, a stage of pronounced
exhaustion arose, characterized by irreversible changes in the hypo-
thalamo-hypophysio-adrenal system.
Hence, the applied regime of 12 hours' hypokinesia during the
most active period of the body's physiological rhythms has as per-
nicious an effect on the latter as the regime of more protracted
daily maintenance of the animals in conditions of restricted motor
activity. The young developing rat body is not capable of restruc-
turing and adapti,ig to a new rhythm of vital function. As a result,
a stressful state develops, exhausting the defensive and adaptive
potential of the body and capE-ble of causing its death.
^G y /^G N? 	 VA A Cile 8 NO >/	 D LO 0 76
5


State of the body in disorders of diurnal physiological rhythms and long-term hypokinesia

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