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Abstract

Swiss-Webster strain mice were administered 'lead' at the doses of 0.1 and 0.2% (w/v) in their drinking water. Treatment started from postnatal day I (PD1) after delivery until PD15. The mothers were then switched to plain tap water. The treated pups showed a decline in their body weight gain. Further, the opening of their eyes and appearance of their body hairs were also delayed. A gradual suppression in the development of the early sensory motor reflexes of the treated pups was also observed. Alterations in the levels of total acid and alkaline phosphatases in the liver, and acetylcholinesterase in the brain tissues were noticed in the developing treated offspring. The 'Tube Restraint Test' of the female offspring, showed alterations in their latency to first bite as well as the number of bites. Almost all behavioural indices of 'Locomotory Test' were significantly increased in the male treated offspring. The toxicity of lead is discussed in the light of the developmental stages of the offspring.
Effect Of Postnatal Lead Exposure On The Development And
Behaviour Of Mice Offspring
Jamaan S. Ajarem, Qasim M. Abu- Taweel and Mohammad Ahmad
Department a/Zoology, College a/Science, King Saud University,
P.o. Box 2455, Riyadh - 11451, Saudi Arabia.
Abstract. Swiss-Webster strain mice were administered 'lead' at the doses of 0.1 and 0.2% (w/v) in their
drinking water. Treatment started from postnatal day I (PD1) after delivery until PD15. The mothers were
then switched to plain tap water. The treated pups showed a decline in their body weight gain. Further, the
opening of their eyes and appearance of their body hairs were also delayed. A gradual suppression in the
development of the early sensory motor reflexes of the treated pups was also observed. Alterations in the
levels of total acid and alkaline phosphatases in the liver, and acetylcholinesterase in the brain tissues were
noticed in the developing treated offspring. The 'Tube Restraint Test' of the female offspring, showed
alterations in their latency to first bite as well as the number of bites. Almost all behavioural indices of
'Locomotory Test' were significantly increased in the male treated offspring. The toxicity of lead is
discussed in the light of the developmental stages of the offspring.
Key words: Lead;postnatalexposure;miceoffspring;sensorymotorreflexes;phosphomonoesterases;brain;liver;
behaviour.
The adverse impact of heavy metal 'lead'
on the developing organisms have been
extensively studied. These studies with animal
models are an important complement to studies
of human subjects, which are by necessity
more observational in designs (Laughlin,
1986). Many investigators have studied the
influence of lead on behavioural activities both
in humans (Bellinger et aI., 1984; Emhart et
aI., 1985; Singh and Ashraf, 1989; Rothenberg
et al., 1989; McMichael et al., 1992) and in
animals (Levin and Bowman, 1983, 1986;
Laughlin et aI., 1983; Donald et aI., 1987;
Draski et aI., 1989; Davis et al., 1990; Ajarem,
1999).
Early postnatal lead exposure in
experimental rats may be the most appropriate
animal model for exposure that occurs
prenatally in humans. Thus, to mimic human
prenatal exposure to a potential teratogen
during a period comparable in rate of brain
development would require postnatal exposure
in the rat (Laughlin, 1986). A major portion of
brain cells (70%) of the closely related rats are
known to be formed postnatally after birth
(Patel, 1983). Several reports are available for
the behavioural effects in offspring associated
with postnatal lead exposure in rats (Sobotka
and Cook, 1974; Grantetal., 1980; Baraldi et
al., 1988; Ferguson et al., 1998) and mice
(Rafales et al., 1979; Draski et al., 1989).
The aim of the present study was to assess
the effect of lead exposure to the offspring
through their mother's milk from birth to
postnatal day 15 (PD 15), on the early
development of reflexes and level of enzyme
activities in brain and liver tissues, in the
developing mouse pups from PD 1 to weaning
at PD21. Furthermore, the locomotory test and
tube-restraint test were also carried out in the
young adult offspring after their weaning
period.
Experimental animals:
Male and female Swiss-Webster strain
mice (8-9 weeks old) were housed in opaque
plastic cages (three females to one male in each
cage) measuring 30 X 12 X 11 cm, in the
animal facility of the Zoology Department,
King Saud University, Riyadh, Saudi Arabia.
Animals were kept under reversed lighting
conditions with white lights on from 22.30 to
10.30 hours local time. The ambient
temperature was regulated between 18 and
noe.
After pregnancy (appearance of vaginal
plug was considered as day one of pregnancy),
the males were removed from the cages and the
females were subjected to experimental
treatments. Food (Pilsbury's Diet) and water
were available ad libitum, unless otherwise
indicated.
Lead administration:
Lead acetate (analytical grade, Riedel de
Haen, Germany) was dissolved in deionized
distilled water in concentrations of 0.1 and
0.2% (w/v), containing 550 and llOOppm of
lead respectively. These lead doses formed the
sole drinking fluid source for the experimental
group of dams during the postnatal period of
the experiment. The drinking fluid containing
lead doses were changed with fresh prepa-
rations every five days. The control group
received deionized distilled water only. In
order to preclude the precipitation of insoluble
lead salts, 1-2 drops of acetic acid (vehicle of
lead) were added to all bottles (including
controls). No "vehicle control" group was
included in this study. All pregnant mice were
housed individually. Treatment of mothers
was started after the delivery of offspring from
the day 1 (PDl) and was continued until
postnatal day 15 (PD15) and thereafter the
mothers were switched to plain deionized
distilled water.
Behavioral observations:
On the day of birth (postnatal day 0, PDO)
the pups were culled to only eight per dam and
were left with their mothers until PD22. During
this weaning period, three pups of each litter
were colour marked from the others and were
subjected to various behavioral tests (described
below) under dim lighting (ca 8 lux). In all, 21
pups belonging to seven litters from each
treatment category were considered. All
observations were recorded on PD 1 and
repeated every other day until PD21 in the
same three colour marked pups of each litter.
These observations were used to measure the
early development of sensory motor coordi-
nation reflexes together with morphological
development in the pups. For statistical
analysis, the mean of all three colour marked
pups per litter was considered as a single score.
Thus, seven replicates from each treatment
category were considered in these obser-
vations.
Body weight: Weight is an useful indicator of
development. Thus, the pups were weighed
every alternate day from PD 1 until PD21.
Righting reflex: The time taken by a pup
placed on its back to turn over and place all
four paws on the substrate was recorded. An
upper limit of 2 min being set for this test.
Cliff avoidance : Pups were placed on the
edge of a table top with the forepaws and face
over the edge. The time taken by the pup to
back away and turn from the "cliff' was
recorded. Again an upper limit of 2 min was
chosen. A latency of 2 min was attributed
when the animal fell from the "cliff'.
Rotating reflex : The surface used to measure
the rotating reflex was the same as that used
for righting reflex, except that it was inclined
at an angle of 30°. The pups were placed on
this surface with their heads pointed
downwards. The time elapsed until the pup
rotate its body through 180° geonegatively and
face its head upwards, was recorded as the
rotating time. The upper limit of this test was
also set at 2 min.
Eye opening and hair appearance: The day
at which the body hair fuzz appeared, and the
eyes opened were also recorded. These two
parameters are also useful morphological
indicators of development.
Locomotory Tests of young adult males:
The offspring were weaned on PD21 and
thereafter, the males and females were isolated
and kept in groups of two or three, for 14 days.
Subsequently, 10 males from each treated
group (including representatives from each 7
litters) were subjected to locomotor
activity tests. The young adult males were
placed in an experimental wooden arena
measuring 80 X 80 X 30 cm and the floor was
divided into 64 equal sized squares. Various
behavioral elements were observed as
described by Ajarem (1987). Elemtnts of
locomotory activity included the number of
squares crossed and the number of wall rears
as well as the duration of locomotion and
immobility. The visual observations in the
arena lasted 300 sec for each animal.
Tube restraint test of young adult females:
The females isolated after weaning period
were subjected to the tube restraint test. Ten
females from each treated group (including
representatives from each 7 litters) were used
for this test. The apparatus was based on the
equipment described by Ajarem and Ahmed
(1992) and consisted of a cylindrical trans-
parent perspex tube 13 cm in length and with
an internal diameter on. 1 cm. One end of the
tube was blocked by a perforated perspex wall
through which a 2 cm long metal target was
attached to a telegraph key/electronic counter
arrangement. This enabled one to record the
number of bites directed by the restrained
mouse towards the target. The test was
conducted visually as outlined by Ajarem and
Ahmad (1994) for 500 seconds under normal
laboratory white lighting and temperature.
Biochemical Studies:
During the weaning period, on PD7, PDI4,
and PD21, one pup was picked up at random
from each litter, apart from those three colour
marked pups that were used for the behavioural
tests. Thus, seven pups were collected from each
experimental group on each postnatal day (PD7,
14 and 21) without any consideration to its sex
and were killed by decapitation. Their brain and
liver were removed and gently rinsed in
physiological saline (0.9% NaCl), and then
Median number (with ranges) of acts and postures
Nwnberof Locomotion Immobility
Squares Wall Rears Wash Duration Duration
crossed Rears cleaning (sec) ( sec )
156 27 2 13 134.6 165.4
(123 - 246) (14 - 36) (0 - 8) (5 - 22) (89.3 - 235.7) (64.3 - 210.7)
201 34 4 7 175.1 124.9
(136 - 237) (19-38) (0 - 7) (0 - 12) (170.3 - 204.3) (95.7 - 129.7)
250 ••• 40 ••• 13 •• 3 •• 245.5 ••• 54.5 •••
(196-255) (35 - 43) (2 - 15) (I - 18) (153.5 - 253.7) (46.3 - 147.5)
Treatment
Group
blotted on Whatman filter paper. Their fresh
weights were recorded, and organs were then
frozen.
Tissue homogenate preparation: A 10% (w/v)
homogenate of each frozen tissue was prepared
10
teflon-glass homogenizer at 4±loC,
centrifuged at 1000 X g for 10 min to remove
cell debris and the supernatant was used for
enzyme assays. The brain homogenate was
prepared in an ice-cold phosphate buffer
(0.067M, pH7.2) and the liver was homogenized
in chilled 0.25M sucrose solution.
Enzymes estimations: The acetylcholinesterase
(AChE) activity in the homogenised brain tissue
was estimated by the method ofHestrin (1949)
using acetylchloline chloride as the substrate.
The specific activity of AChE was expressed as
I..l
moles acetylcholine chloride hydrolysed per
gram wet tissue weight per hour at 37 ± 1°C.
The levels of total acid phosphatase (AcP)
and alkaline phosphatase (AlP) were estimated
in the liver tissue homogenates using sodium p-
nitrophenol phosphate as the substrate
(Bergmeyer et ai., 1974). The protein content in
the homogenates was estimated according to the
method of Lowry et ai. (1951). The specific
activities of these phosphomonoesterases were
expressed as n-moles p-nitrophenolliberated per
mg protein per minute at 37 ± 1°C.
Statistical Analysis :
The data of body weight, dates of
morphological developments, data of sensory
motor reflexes and data of biochemical
analyses were compared within the
experimental groups by the analysis of
variance (ANOYA) using minitab computer
programme, and were subsequently analysed
by Student's t-test (Yamane, 1973). Data of
locomotory test and tube restraint test were
compared within the experimental groups by
the analysis of variance (ANOYA) and
Latency to first bite (see) Number of bites
9 73
( 3
-
20 ) ( 18
-
90 )
24 39
( 2
-
150)
(13
-64)
III *** 29 **
( 21
-
260 ) ( I
-
65 )
** and ***indicate statistically significant at p< 0.01 and p<O.OOI respectively from the control by Mann-
Whitney V-test.
subsequently were analysed using Mann-
Whitney V-tests (Sokal and Rohlfe,1981).
The mean body weight of the control and
treated groups of pups, were almost similar on
the day of their birth. However, thereafter, the
mean body weight gain of the treated groups
started showing a decline (p<O.OOI) from P03
onwards throughout the weaning period upto
P021 as compared to the controls (Fig. I).
The morphological developments, like
eye opening and body hair appearance,
were also affected by lead treatment (Fig.2).
The body hair appearance and the eye opening
of the lead-treated group of pups were delayed
significantly (p<O.00 I) as compared to the
controls.
Postnatal exposure of dams to lead, had a
significant and dose-dependent effect on the
development of all the sensory motor reflexes
in the pups in the present study. Pups exposed
to lead through the milk of the treated mothers
started showing lethargic and sluggish reflexes
from P03 onwards. Throughout the postnatal
developing period, lead had a significant
suppressive effect on the righting reflex
(p<O.OOI) as shown in Fig.(3). The rotating
reflex (Fig.4) and the cliff avoidance activity
(Fig.5)
III
the treated pups were also
significantly (p<O.OOI) suppressed throughout
their weaning period, upto P021. Significant
interactions between the postnatally developing
age and lead doses were also seen. The higher
dose was more suppressive affecting all the
reflexes measured in the present study.
The level of AcP (Fig. 6) and AlP (Fig. 7)
activities in liver of the control pups were low
at P07 stage, but increased as the weaning age
of the pups increased. Pups exposed to lead
during the postnatal weaning period, had
increased level of these phosphomonoesterases
activities at both doses of the lead, in their liver
at all developing stages (Figs. 6 and 7).
The level of AChE activity increased
gradually in the brain of the control pups as
their weaning age increased (Fig. 8). Postnatal
lead exposure at both the doses, caused a
biphasic influence on this enzyme at various
15
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en
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--Control
····0····
0.1%
w/v
~- O.2%w/v
5 7 9 11 13 15 17
Age of developing pups (in days)
Fig. 1: Effect of postnatal lead exposure on the mean body weight gain of the mouse pups.
**
and
***
indicate significance atp< 0.01 and p< 0.001 , respectively, as compared
to control (by Student's t-test).
w
en
,·1 15
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>-
III
"0
'0
~
~ 10
E
::I
c:
c:
III
Q)
5
:!
c:::::::J
Control
i,**~'l0.1
%
w/v
-O.2%wlv
Fig. 2 : Effect of postnatal lead exposure on the hair appearance and eye opening in the mouse pups.
***
indicates significance at p<0.001 as compared to control (by Student's t- test).
w
(J)
45
+1
en
"0
40
c:
o
~ 35
en
c:
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::.
-Control
_0-_
0.1 %
w/v
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***
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*7/
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,,*.:-....
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A \ \
// ***......... \
i
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/
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en
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e
30
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c:
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.B
20
e
c:
~ 10
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5 7 9 11 13 15 17
Age of developing pups (in days)
Fig. 3: Effect of postnatal lead exposure on the mean righting reflex of the mouse pups.
*, ** and *** indicate significance at p<0.05, p<O.Ol and p<O.OOl, respectively,
as compared to control (by Student's t-test).
-Control
._--<:>- •••
0.1 %
w/v
- .•- 0.2%
Wlv
5 7 9 11 13 15 17
Age of developing pups (in days)
Fig. 4: Effect of postnatal lead exposure on the mean rotating reflex of the mouse pups.
*, ** and *** indicate significance at p<0.05, p<0.0l and p< 0.001, respectively,
as compared to control (by Student's t-test).
postnatal developing stages (Fig. 8). At PD7
and PD14, the enzyme was inhibited
(p<O.OOI), whereas at PD21 the enzyme was
stimulated (p<O.001)
The results of locomotor activity test
(Table 1) have shown that postnatal lead
exposure has a significant stimulatory effect at
the higher dose only. The numbers of squares
crossed, wall rears, rears, as well as the
duration of locomotion in the weaned male
offspring increased significantly (p<O.OOl).On
the other hand, the number of wash and the
duration of immobility had significantly
decreased (p<O.001) in the animals exposed to
lead at higher dose only, as compared to that of
controls.
The data of 'tube-restraint' test (Table 2)
showed that the latency to first bite as well as
the number of bites on the target, were
decreased significantly (p<O.001), only in the
male offspring that were exposed to the higher
dose of lead concentration.
The results of the present study have
clearly demonstrated that the dams exposed
to lead, postnatally from PDl to PD15,
caused a low level of lead exposure to the
developing pups, by way from their mother's
milk supply. Such treated pups markedly
differed from their controls in the rate of
physical maturation, sensory motor develop-
ment, biochemical alterations in the level of
esterases in the developing liver and brain,
locomotory and tube-restraint test behaviour of
the young adult offspring. Such significant
effect of lead has previously been reported in
rodents (Grant et al., 1980; Draski et al., 1989;
Ferguson et al., 1998).
Postnatal lead exposure has suppressed
the preweanling reflexes in the developing
mice pups. The righting and rotating reflexes
as well as the cliff avoidance were significantly
delayed as compared to their controls. Further,
the effects on reflexes clearly suggests for a
direct intervention of lead with the developing
pups because it is likely that the pups received
lead via their mother's milk during lactation. It
IS now well documented that significant
quantities of compounds that are given to
mothers during late pregnancies and postnatal
period, may be transmitted to the offspring
in
utero and lor via mother's milk during
lactation (Ordy et al., 1966; Fabro and Sieber,
1969; Mereu et al., 1987; Draski et al., 1989;
Ajarem and Ahmad, 1991; 1998a and b;
Ajarem, 1999).
Abnormalities in response to teratogens
may be due to several factors that causes
alterations
III
normal cell metabolism,
especially in enzymes and their substrates
(Wilson, 1973), or due to combination of
several factors (Coyle et al., 1976). The hepatic
enzymes AcP and AlP are known good
indicators of liver status (Corpas et al., 2001)
and are frequently associated with transport
mechanisms across the biological membranes
(Starling, 1975, Ajarem and Ahmad, 1991). In
rodents, lead level in maternal milk correlates
with lead level in the blood of developing pups
(Palminger and Oskarsson, 1993). Thus,
alterations in the level of these phosphomo-
noesterases in liver of the developing pups, due
to postnatal lead exposure, might have led to
variations in their phosphate pool. This
probably lead to disturbed energy source
available to the animal with the consequent
disturbance in its metabolism (Wilson, 1973),
which is reflected in the form of altered
physical maturation and sensory motor
reflexes.
60
-
w
(J)
+1
fI)
50
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C
0
(.)
Q)
40
II)
.5
-
Q)
(.)
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c
eu
"C
'0
>
20
eu
!I:
u
c
10
eu
Q)
:E
0
-Control
····0····
0.1%
w/v
- .•- 0.2% wlv
5 7 9 11 13 15 17
Age of developing pups (in days)
Fig. 5: Effect of postnatal lead exposure on the mean cliff avoidance activity of mouse pups.
**
and
***
indicate significance at p<O.O1 and p< 0.001 , respectively,
as compared to control (by Student's t-test).
0)
.E
u
500
" 0
,S'\""'
e!+1
(I)"'"
:e ~
400
-111
o:E
Cw
1!
en
300
Q.
+1
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'E
E200
6.£
lI)J!!
..9!e
o
Q.
100
E
C
c=JControl
_O.1%w/v
_O.2%wlv
7.0 14.0 21.0
Age of developing pups (in days)
Fig.6: Effect of postnatal lead exposure on the activity of AcP in liver of the mouse pups at various
developing weaning ages.
*
and
***
indicate significance at
p<O.OS
and
p<
0.001, respectively,
as compared to control (by Student's t-test).
300
c:::J Control
0)
_0.1%wlv
.EO
250
•• 0.2% wlv
't:I
o
.$ .•.•
frt'
!M
200
=1G
O::E
eW
150
Q)(/)
-a+t
e.5
:l:lE
100
Te
Q..-
J~
~Q.
50
e
07.0 14.0 21.0
Age of developing pups (in days)
Fig. 7: Effect of postnatal lead exposure on the activity of AlP in liver of the mouse pups
at various developing weaning ages.
*, ** and *** indicate significance at p<O.OS, p<O.Ol and p< 0.001, respectively,
as compared to control
(by
Student's t-test).
100
•..
c:::J Control
:I
90
1iBI0.1%wlv
Q)0
•• 0.2% wlv
~~
80
00)
:C'ijj0
70
~ ~ 0
eQ) .•••
60
=iilrt'
°
11IM
~:p
50
u
1G
i'ii::E
40
~w
CUi(/)
III +1
30
J!III
0>-
20
E-
::le
't:I
>-
10
~
07.0 140 21,0
Age of developing pups (in days)
Fig. 8: Effect of postnatal lead exposure on the activity of AChE in brain of the mouse pups
at various developing weaning ages.
*** indicates significance at p< 0.001, as compared to control
(by
Student's
t-test).
An important neurotransmitter that has
been implicated in behaviour porcess is AChE
(Allikmets, 1974). Changes in the behaviour
due to toxicants are presumably due to
alterations in the availability of neurotrans-
mitters (Kruck and Pycok, 1979; Kellog et al.,
1980; Lee, 1980). It was found in the present
study that, the level of AChE in the brain of the
control pups increased gradually as their
weaning age increased. This may be possibly
because it is known that a major portion of
brain cells (70%) of the closely related rats are
formed after birth (Patel, 1983). Further, an
inhibition in the level of AChE was detected in
the lead exposed pups on PD7 and PD 14. This
could possibly explain as to why the sensory
motor reflexes are subsided gradually during
the first fortnight of their postnatal
development. Also, it has been established that
the cerebellum in the brain may be most
vulnerable to the neurotoxicity of lead in the
the very rapid growth period during the first 20
postnatal days (Gietzen and Woolley, 1984).
Thus, lead could have produced developmental
abnormalities in the brain as well as an
alteration in the level of AChE, that might have
brought about the observed effects on the
motor reflexes of the developing pups in the
present study. It has been reported that
alterations in brain enzymes are among the
factors responsible for disturbances in
behavioural activities of affected animals
(Branchey and Friedhoff, 1976; Kellog
et al.,
1980; Johnson
et aI.,
1981; Ajarem and
Ahmad, 1991).
The locomotory test on the male offspring
and the tube restraint test on the female
offspring after the weaning period, at the
adulthood stage, suggest for a lasting and
significant effect in their behavioural activities
brought about by postnatal lead exposure. The
male offspring at the adolescent age show
hyperactivity (anxiogenic effect) in their
locomotory test. The female offspring, on the
other hand, show a decline in the tube restraint
test which reflects for an anxiolytic effect of
lead. However, since the results of tube
restraint test are deemed to be somewhat
controversial (Brain
et al.,
1983), further
studies are needed to confirm such anxiolytic
effect of lead in female offspring.
The present results strongly support the
earlier conclusion of Ajarem and Ahmad
(1991, 1998) that the enzymes AcP , AlP and
AChE could be used as convenient markers in
teratological studies of adults as well as the
developing pups during the weaning period.
Further, the present results also support the
earlier findings (Peters
et al.,
1994; Flora and
Seth, 2000) that lead exerts neurotoxic effects
by altering certain membrane bound enzymes
and may cause oxidative stress which
ultimately alters the cellular processes. Such
effects might be affecting the overall
morphological developments and sensory
motor reflexes of the developing pups, and
behaviour of the young adult offspring.
The authors are grateful to The Chairman,
Department of Zoology, of this University, for
providing all necessary laboratory facilities ..
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... The nervous system is the primary target for the low levels of Pb exposure and the developing brain is extremely sensitive to the toxic effects of Pb during the prenatal (gestational) period (Needleman and Gatsonis, 1990; Zawia et al., 1998; Reddy and Zawia, 2000; Chetty et al., 2001; Basha et al., 2003; Huang and Schneider, 2004, De Marco et al., 2005). Thus, chronic exposure to Pb during perinatal or early postnatal period produces central nervous system impairments as indicated by behavioural, physiological and biochemical measures (Ernhart and Greene, 1990; Lanpear et al., 2000 Lanpear et al., ,2001 Antonio et al., 2003; Ajarem et al., 2003). However, such studies in experimental animal models during prenatal exposure (exposure during early gestational development) is very limited (Leret et al., 2003). ...
... Further, the effect on reflexes clearly suggests a direct intervention of lead with the developing fetus and it is likely to assume that the pups received lead via their mother's blood supply in utero. It is now well documented that significant quantities of some compounds that are given to mothers during late pregnancies and postnatal period, may be transmitted to the offspring in utero and /or via mother's milk during lactation (Fabro and Sieber, 1969; Mereu et al., 1987; Draski et al., 1989; Ajarem and Ahmad, 1991; 1998a and b; Ajarem, 1999; Ajarem et al., 2003). Multiple factors are involved for the causal abnormalities in response to teratogens that ultimately induces alterations in normal cell metabolism, especially in enzymes and their substrates (Wilson, 1973), or due to combination of several factors (Coyle et al., 1976). ...
... Thus, lead produced developmental abnormalities in the brain as well as disturbance in the level of AChE, that might have caused the observed effects on the motor reflexes of the developing pups. It has been reported by some authors that alterations in brain enzymes are among the factors responsible for disturbances in behavioural activities of the affected animals (Branchey and Friedhoff, 1976; Kellog et al., 1980; Johnson et al., 1981; Ajarem and Ahmad, 1991; Ajarem et al.,2003). The locomotory test on the male offspring after the weaning period, at the adolescent stage, showed a significant effect in their behavioural activities brought about by prenatal lead exposure and showing hyperactivity in their locomotory test. ...
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Swiss-Webster strain laboratory mice were administered ‘lead’ at the doses of 0.1 and 0.2% (w/v) in their drinking water. Treatment started from day 1 of pregnancy and was continued until the day of delivery. The mothers were then switched to plain tap water. The treated pups showed a decline in their body weight gain from the postnatal day 1 (PD1) of their birth until PD21 throughout the weaning period. Further, the opening of their eyes and appearance of their body hairs were also delayed. A gradual suppression in the development of the early sensory motor reflexes of the treated pups was also observed. A gradual increase in the levels of total acid and alkaline phosphatases in the liver, and alterations in the acetylcholinesterase activity in the brain tissues was noticed in the developing treated offspring. Almost all behavioural indices of ‘Locomotory Test’ were significantly increased in the male treated offspring, except the number of wash cleaning and immobility duration, that were significantly decreased. The toxicity of lead is discussed in the light of prenatal lead exposure and the developmental stages of the treated offspring .
... Chronic postnatal Pb exposure at a high concentrations (500 ppm) (blood Pb level∼70 µg/dL measured after 70 days of exposure) starting at weaning (21 days age) and lasting into adulthood (total 70 days of exposure) resulted in an anxiogenic effect observed in male but not female Swiss mice (Soeiro et al., 2007). An anxiogenic effect was also observed in adolescent male but not female mice after early postnatal Pb exposure (birth to PND15) but again, only with high level exposures (1100 ppm; blood Pb level not reported) (Ajarem et al., 2003). Disruption of olfactory recognition memory tested at PND28 after low (30 ppm) and high (330 ppm) postnatal Pb exposure from birth to PND28 (blood Pb level ranging from 0.02-20.31 ...
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