Naunyn-Schmiedeberg's Archives of Pharmacology
© Springer-Verlag Berlin Heidelberg 2014
10.1007/s00210-013-0955-zOriginal Article
Differential effects of paradoxical sleep deprivation on memory and oxidative stress
Alisson Menezes Araujo Lima1, Veralice Meireles Sales de Bruin1 , Emiliano Ricardo Vasconcelos Rios2 and Pedro Felipe Carvalhedo de Bruin1
(1)
Programa
de Pós-Graduação em Ciências Médicas, Faculdade de Medicina,
Universidade Federal do Ceará, R. Cel Nunes de Melo 1315, Rodolfo
Teófilo, 60.430-270 Fortaleza, Ceará, Brazil
(2)
Programa de Pós-Graduação em Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Brazil
Received: 11 July 2013Accepted: 25 December 2013Published online: 15 January 2014
Abstract
Sleep has important functions for
every organ in the body and sleep deprivation (SD) leads to disorders
that cause irreparable damage. The aim of this study was to investigate
behavioral and brain structural alterations in mice deprived of
paradoxical sleep for 48 and 72 h. Working memory, aversive memory
as well as levels of nitric oxide (NO) and thiobarbituric acid reactive
substances (TBARS) in the hippocampus, body striatum, and prefrontal
cortex were evaluated. Working memory was affected in the 48- and 72-h
SD groups while aversive memory was altered only in the 48-h SD group (p ≤ 0.05). Our findings showed that SD reduces NO levels in most brain areas (p
< 0.05): NO levels were unaltered in the striatum of animals
sleep-deprived for 48 h. Higher levels of TBARS were observed in
all areas of the SD groups (p ≤
0.05). Thus, we confirmed that SD has duration-dependent effects on
behavior as well as on NO and TBARS levels in the brain. Preserved
striatum NO levels suggest that this structure is less vulnerable to
oxidative stress and is only affected by SD of longer duration.
Increased TBARS and reduced NO levels in the hippocampus and prefrontal
cortex confirm a central role for both these structures in working
memory and aversive memory. Contextual fear conditioning was not
affected by longer periods of SD. Thus, our findings suggest that
shorter SD time may be more beneficial to avoid aversive memory where
this may have implications for the management of posttraumatic stress.
Keywords
Paradoxical sleep deprivation
Oxidative stress
Nitric oxide
TBARS
Aversive memory
Striatum
Introduction
Sleep is essential for the
consolidation of memory besides numerous other health-related functions.
This is a complex process: evidence shows that sleep influences memory
consolidation depending on type of memory, psychological conditions, and
expected reward gain, among other factors (Diekelmann et al. 2009).
Specific circuitry may possibly be involved and it has been
hypothesized that prefrontal-hippocampal circuitry is essential for
memory consolidation during sleep (Diekelmann et al. 2009; Varela et al. 2013).
Recently, it has been suggested that reuniens cells located in the
thalamus directly coordinate activity in medial prefrontal cortex and
hippocampus and are important for memory consolidation (Varela et al. 2013).
It has been previously demonstrated that sleep deprivation increases oxidative stress in the brain (Vollert et al. 2011; Alzoubi et al. 2012).
Several studies have confirmed that the effects of sleep deprivation
are at least partially mediated by reactive oxygen species (ROS)
(Ramanathan et al. 2002; Brown and Naidoo 2010).
In fact, sleep deprivation induces noxious metabolic and immunological
alterations that eventually lead to lethal consequences and it is
thought that antioxidant imbalance mediates these alterations (Everson
et al. 2005). A theory that sleep removes free radicals accumulated in the brain during wakefulness has been proposed (Reimund 1994).
Understanding how memory and different parts of the brain are affected
by oxidative stress following sleep deprivation is a subject that
warrants further elucidation.
Evidence suggests that an
interruption in the nitric oxide (NO)/cyclic guanosine monophosphate
(cGMP) pathway signaling dopamine can decrease the regulation of the
NO/cGMP/CREB (Thatcher et al. 2006).
This latter binding protein is essential for the cAMP response involved
in the process of learning and memory. Thus, a direct connection between
NO and learning/memory function exists. Given that free radicals, which
include reactive nitrogen and reactive oxygen species, are hard to
measure because of their extreme reactivity, NO levels can be
secondarily deduced from levels of its metabolites, nitrates/nitrites.
Notably, NO is the only endogenous source of brain nitrates and
nitrites, because dietary nitrates and nitrites do not cross the
blood–brain barrier (Ramanathan et al. 2002).
Nitrite is a stable compound that has been frequently used as a marker
of NO production; however, it only reflects the summation of the events
occurring for nitric oxide in a given time window (Clement et al. 2004).
When antioxidants are incapable of scavenging the free radicals, lipids
will suffer oxidative damage and express thiobarbituric acid reactive
substances (TBARS) (Ramanathan and Siegel 2011).
Some studies have reported the role of NO in regulating the sleep-wake cycle, probably by homeostatic processes (Kapas et al. 1994; Dzoljic et al. 1997; Burlet et al. 1999; Clement et al. 2004).
Previously, a subset of cortical neurons, GABAergic interneurons, that
express neuronal NO synthase have been related to slow-wave activity
(Gerashchenko et al. 2008). Cortical
neurons immunoreactive for neuronal NO synthase and the neurokinin-1
receptor have been proposed to be involved in this physiological process
(Wisor et al. 2011; Morairty et al. 2013).
Moreover, sleep deprivation has been shown to increase the expression
of NO synthase in prolonged wakefulness-active neurons labeled by Fos.
The increase of NO synthase expression in wakefulness-active neurons has
been positively correlated with sleep pressure, suggesting a role for
NO-producing cells in the homeostatic control of sleep (Kalinchuk et al.
2010).
Clinical and/or biochemical factors, such as nutrition (Vazquez-Medina et al. 2012), physical activity (Nielsen et al. 2007), neurotransmitter abnormalities (Das et al. 2008), and cytoskeletal protein damage (Rodriguez-Vazquez et al. 2012) have been implicated in the genesis of neuronal damage (Zhang et al. 2010).
In fact, the response or adaptation to sleep deprivation is a complex
process under multifactorial influences including the use of medications
that affect neurotransmission (de Oliveira et al. 2004).
The duration of sleep deprivation is one of the factors that may induce
differential cerebral alterations. For instance, a study has shown that
seals use an adaptive mechanism of hormetic response to intermittent
hypoxia and increased oxidative stress (Vazquez-Medina et al. 2012).
Moreover, time-specific effects of sleep deprivation on cytoskeletal
protein damage have been shown (Rodriguez-Vazquez et al. 2012).
Considering this body of evidence and the possibility that adaptive
response to oxidative stress may occur, it follows that the duration of
paradoxical sleep deprivation may differentially affect memory and
oxidative stress in the various parts of the brain. The aim of this
study was to evaluate memory function and levels of nitrite and TBARS as
indicators of oxidative stress and lipid oxidative damage in various
different brain areas in mice subjected to paradoxical sleep deprivation
for 48 and 72 h.
Materials and methods
Animals
Adult Swiss albino male mice,
weighing between 25 and 30 g, were used. Animals were kept in
plastic cages, in groups of five, lined with wood shavings; exposed to a
natural 24-h light/dark cycle; and fed standard chow and water ad
libitum. The study followed the ethical principles of animal
experimentation established by the Brazilian College of Animal
Experimentation (COBEA) and was previously approved by the Ethics
Committee in Animal Research (CEPA-67-09).
Paradoxical sleep deprivation
The methods used to induce REM deprivation was based on the multiple platform method adapted for mice. van Hulzen and Coenen (1981)
introduced the multiple platform method using several platforms in a
large water tank, reducing the movement restriction stress induced by
the single platform technique (van Hulzen and Coenen 1981).
In the present study, the multiple platform method was further
modified. Five platforms (5 cm in diameter), placed in a tank
(40 × 30 cm) filled with water to within 1 cm of the upper
surface of the platforms, were used. Five mice, taken from the same cage
in which they were previously housed, were placed in each tank for 48
or 72 h, with water and food ad libitum. The method consists of
placing the animals in a compartment with several narrow platforms
surrounded by water. Once accustomed to these conditions, the animals
can achieve slow-wave sleep, whereas REM sleep is restricted. The loss
of muscle tone associated with sleep deprivation results in animals
touching the water and awakening. This multiple platform model does not
impose restriction of movement or social isolation (Patti et al. 2010).
Experimental protocol
Experimental procedure animals were distributed into three groups (N
= 8 each). Mice were submitted to 48- or 72-h paradoxical sleep
deprivation or kept in their home cages for control. Behavioral tests
were performed in all groups and after paradoxical sleep deprivation in
the 48- and 72-h groups. Animals were decapitated immediately after
behavioral tests (15 min), and the striatum, hippocampus, and
prefrontal cortex were then dissected and frozen for analysis. All
behavioral tests, the Y-maze (8 min) and step-down (5 min),
were performed immediately after the end of sleep deprivation in the 48-
and 72-h groups. The tests were conducted during daytime, under
conditions of darkness, from 8:00 am to 9:00 am. Immediately
after the behavioral tests (13 to 15 min), animals were sacrificed
and brain tissue was collected.
Behavioral tests
Assessment of working memory—Y-maze test
Working memory was assessed by
the Y-maze test. In this test, the animals are placed in a Y-shaped
maze with three arms of equal length (Sarter et al. 1988).
Typically, the animals have a strong tendency to switch entries in
different environments. For the evaluation of memory, arms are numbered.
Initially, the animal is placed in the apparatus for 8 min and the
number of entries into each arm is noted. This is considered a settling
time during which animals enter three different arms without
repetition. The results are expressed as percentage and obtained through
a mathematical formula (Hidaka et al. 2011).
The success of the test is indicated by the high switching rate in the
control groups, indicating that the animals cannot remember which arm
they entered last. Between each session, the maze is cleaned with a
20 % alcohol solution and dried using paper towels.
Evaluation of aversive memory—step-down test
One way to assess the conditioned response to fear is through the passive avoidance test (DeNoble et al. 1986).
During the test, inhibition of the animal’s natural tendency to descend
onto the lower platform due to the presence of an aversive component
constitutes a conditioned response. For this test, animals were
previously trained. They were placed in the portable housing for the new
environment (1 min), training (5 min), and subsequent test
(15 min, evaluating short-term memory) procedures. For the analysis
of delayed recall, the animals were subjected to the test (5 min)
again after 48 and 72 h (with and without sleep deprivation).
Nitrite levels in the sample
This method is based on the use
of the Griess reagent which detects the presence of nitrite in the
sample through a diazotization reaction by formation of a chromophore
pink color. The reagent is prepared using equal parts of 5 %
phosphoric acid, N-1-naphthalenediamine (NEED) 0.1 %, 1 %
sulfanilamide in 5 % phosphoric acid, and distilled water. The
assay was performed by the addition of 100 μL of the supernatant of
the homogenate at 10 %, comprising potassium phosphate buffer in
100 μL of Griess reagent, to the white 100 μL in 100 μL
of reagent buffer. The standard curve was obtained through serial
dilutions (100, 50, 25, 12.5, 6.25, 3.12, 1.56 μM) of nitrite. The
entire assay was performed in a 96-well plate and absorbance readings
taken in the 560-nm range (Patti et al. 2010).
Determination of lipid peroxidation
The rate of lipid peroxidation
was estimated by determination of malondialdehyde (MDA) using the TBARS
test. The samples were washed with cold saline to minimize interference
of hemoglobin with free radicals. All samples were homogenized at
10 % with potassium phosphate buffer, withdrawn at a rate of
250 μL and placed in a water bath at 37 °°C for 1 h.
Subsequently, 400 μL of 35 % perchloric acid was added and
centrifuged at 14,000 rpm for 20 min at 4 °C. The
supernatant was removed and placed in contact with 400 μL of
0.6 % thiobarbituric acid. The resultant mixture was then incubated
at 95–100 °C for 1 h. After cooling, the mixture absorbance
of the supernatant was read at 532 nm. A standard curve was
generated using 1,1,3,3-tetramethoxypropane. Results were expressed as
nanomoles of MDA per milligram of protein (Khadrawy et al. 2011).
Statistical analysis
Descriptive statistics are
presented as mean (±standard deviation), range, and frequency
(percentage values). All data were tested for normal distribution and
equal variance. Analysis of variance (ANOVA) followed by post hoc test
or Student’s t test was employed
to compare results of oxidative stress biomarkers between multiple
groups and between sleep-deprived animals versus controls, respectively.
The Kruskall-Wallis test and Mann-Whitney U
test for continuous variables were used to compare behavioral test
results between multiple groups and between sleep-deprived animals
versus controls, respectively. Statistical analysis was carried out
using SPSS for Windows, version 16.0. Statistical significance was set
at p < 0.05.
Results
Our findings show that sleep
deprivation reduced NO levels in almost all regions studied (with the
exception of the striatum in animals deprived of sleep for 48 h)
and increased TBARS levels in all areas and groups. Working memory was
affected in both of the sleep-deprived groups while aversive memory was
affected only in the group that was sleep-deprived for 48 h.
Animal groups sleep-deprived for 48 (p = 0.002) and 72 h (p = 0.000) showed worse performance on the Y-maze test (Fig. 1).
Animals sleep-deprived for 48 h showed impaired aversive memory as
evaluated by the step-down test. Animals sleep-deprived for 72 h
showed no deficit in aversive memory compared to controls (Fig. 2).
Fig. 1
Effect of
paradoxical sleep deprivation on Y-maze test performance in mice.
Compared to controls, both groups of mice sleep-deprived for 48 (N = 8) and 72 h (N = 8) showed worse performance in working memory as evaluated by the Y-maze test (a,bMann-Whitney test, p < 0.05). The Mann-Whitney test was used for comparison between control and 48 h sleep-deprived groups (a
p = 0.002) and between control and 72-h sleep-deprived groups (b
p = 0.001)
Fig. 2
Effect of
paradoxical sleep deprivation on step-down test performance in mice.
Animals sleep-deprived for 48 h showed worse aversive memory
performance as evaluated by step-down in comparison to controls
(Mann-Whitney test, p = 0.007). Mice sleep-deprived for 72 h showed no deficit in aversive memory compared to controls
Oxidative stress biomarkers
Nitrite titration
Mice submitted to paradoxical sleep-deprived for 72 h showed higher nitrite levels in the striatum (Fig. 3a, p
= 0.004). No significant difference was found in animals sleep-deprived
for 48 h. Both groups of animals sleep-deprived for 48 and
72 h showed higher nitrite levels in the hippocampus (Fig. 3b, p = 0.01 and p
= 0.007, respectively). Higher nitrite values in the prefrontal cortex
were also observed in both these groups of animals (Fig. 3c, p = 0.01 and p
= 0.002, respectively). In the striatum, control animals had higher
values (123.8 μM, standard error (SE) 6.125) compared to animals
deprived of sleep for 48 (92.13 μM, SE 15.73) and 72 h
(64.17 μM, SE 5.247). For the hippocampus, control animals showed
higher levels (96.67 μM, SE 4.592) compared to animals deprived of
sleep for 48 (65.35 μM, SE 5.542) and 72 h (64.88 μM, SE
4.367). In the prefrontal cortex, control animals showed higher values
(117.1 μM, SE 6.196) compared to animals sleep-deprived for 48
(58.58 μM, SE 6.508) and 72 h (65.01 μM, SE 3.729).
Fig. 3
Effects of
paradoxical sleep deprivation on oxidative stress asmeasured by nitrite
levels in striatum (a), hippocampus (b), and prefrontalcortex (c) of
mice. Controls exhibited higher nitrite values in all areascompared to
both 48- and 72-h sleep-deprived mice. Results areexpressed considering
p<0.05 and 95 % CI (ANOVA followed byBonferroni post hoc test)
TBARS titration
Paradoxical sleep-deprived
mice, for both 48 and 72 h, showed significantly lower levels of
TBARS in the striatum, hippocampus, and prefrontal cortex as
demonstrated by Fig. 4.
In the striatum, controls (11.74 μmol, SE 2.285 SE) showed lower
levels compared to 48- (50.17 μmol, SE 3.454) and 72-h
(33.65 μM, SE 2.792) sleep-deprived animals. In the hippocampus,
controls showed lower values (6.955 μmol, SE 0.687) compared to 48-
(40.96 μmol, SE 3.548) and 72-h (38.34 μM, SE 4.250)
sleep-deprived mice. For the prefrontal cortex, controls showed lower
TBARS values (7.183 μmol, SE 0.988) compared to 48-
(37.22 μmol, SE 3.921) and 72-h (39.83 μM, SE 2.033)
sleep-deprived mice. Mean and standard deviation values obtained in this
study are shown in Table 1.
Fig. 4
Effect of paradoxical sleep deprivation on oxidative stress as measured by TBARS levels in striatum body (d), hippocampus (e), and prefrontal cortex (f)
of mice. Controls exhibited lower TBARS levels in the striatum compared
to both 48- and 72-h sleep-deprived mice (ANOVA followed by Bonferroni
post hoc test, p
< 0.05). Controls exhibited lower TBARS levels in the
hippocampus compared to both 48- and 72-h sleep-deprived mice (ANOVA
followed by Bonferroni post hoc test, p
< 0.05). Controls exhibited lower TBARS levels in the prefrontal
cortex compared to both 48- and 72-h sleep-deprived mice (ANOVA followed
by Bonferroni post hoc test, p < 0.05)
Table 1
Descriptive analysis of memory tests (Y-maze and step-down) and biochemical analyses for NO and TBARS in all groups
Control | 48 h PSD | 72 h PSD | |
|---|---|---|---|
Y-maze | 80.83 % (±1.98 SE) | 57.51 % (±3.22 SE) | 66.40 % (±2.72 SE) |
Step-down | 276.4 s (±23.60; 48 h) | 71.80 s (±26.76 SE) | 300.0 s (±0) |
272.0 s (±23.32; 72 h) | |||
Nitrite SB | 123.8 μM (±6.125 SE) | 92.13 μM (15.73 ± SE) | 64.17 μM (±5.247 SE) |
Nitrite HC | 96.67 μM (±4.592 SE) | 65.35 μM (5.542 ± SE) | 64.88 μM (±4.367 SE) |
Nitrite PFC | 117.1 μM (±6.196 SE) | 58.58 μM (6.508 ± SE) | 65.01 μM (±3.729 SE) |
TBARS SB | 11.74 μmol (±2.285 SE) | 50.17 μmol (3.454 ± SE) | 33.65 μM (±2.792 SE) |
TBARS HC | 6.955 μmol (±0.687 SE) | 40.96 μmol (3.548 ± SE) | 38.34 μM (±4.250 SE) |
TBARS PFC | 7.183 μmol (±0.988 SE) | 37.22 μmol (3.921 ± SE) | 39.83 μM (±2.033 SE) |
Discussion
Our findings confirm the
differential effects of paradoxical sleep deprivation on behavior and
oxidative stress in the brain. First, we showed that 48-h paradoxical
sleep deprivation reduced posttraining contextual fear conditioning.
However, contextual fear conditioning was not affected after longer
periods of paradoxical sleep deprivation. These findings suggest that a
shorter paradoxical sleep deprivation time is more beneficial for
avoiding fear conditioning or posttraumatic stress memory. A previous
study indicated that sleep deprivation reduces the development of
posttraumatic stress disorder via extinction of the fear-magnifying
effects of memory (Kuriyama et al. 2010). In agreement with our findings, Graves et al. (2003)
showed that sleep deprivation shortly after training reduced contextual
fear conditioning while sleep deprivation after a longer period of
training had no effect (Graves et al. 2003).
The present findings are also in partial agreement with a previous
report indicating that, unlike longer periods, shorter periods of sleep
deprivation are associated with disruption of memory reconsolidation
(Shi et al. 2011). Our study indicated that a delay in recovery for aversive memory occurs after longer periods of sleep deprivation.
It has been suggested that the
biochemical pathways linked to memory consolidation after sleep,
possibly related to protein kinase A and protein synthesis inhibitors,
are vulnerable to the duration of sleep deprivation (Hellman et al. 2010).
Moreover, it has been demonstrated that a combination of sleep
deprivation with a Western diet elevates TBARS levels and increases
oxidative stress in the hippocampus, thus inducing memory impairment.
These factors, when combined, were reported to produce greater
impairment than each factor alone (Alzoubi et al. 2013). All these findings show that multiple factors affect memory impairment after sleep deprivation.
In this study, nitrite levels were
reduced in the hippocampus and prefrontal cortex in both the 48- and
72-h sleep-deprived groups. In the striatum, nitrite was reduced only in
the 72-h sleep-deprived group. The preservation of striatum nitrite
levels suggests that this structure is less vulnerable to oxidative
stress and is only affected by a longer period of paradoxical sleep
deprivation. Increased TBARS and reduced nitrite levels in the
hippocampus and prefrontal cortex confirm a central role for these two
structures in working memory and aversive memory. Also, in this
experimental model, nitrite levels in the striatum did not play a key
role for working and aversive memory. Lipid peroxidation, based on
analysis of end products such as lipid peroxides, malondialdehydes, and
other low molecular weight aldehydes (TBARS), was increased in all 48-
and 72-h paradoxical sleep-deprived animals and in all the studied areas
including the striatum, hippocampus, and prefrontal cortex.
Considering that paradoxical sleep
deprivation has been shown to have both harmful and beneficial effects
upon several biological functions, we will further discuss the present
and previous findings relating to sleep deprivation, memory, and
oxidative stress. Controversy remains over the effects of sleep
deprivation on oxidative stress products and antioxidants. For instance,
a previous study has shown that long periods of sleep deprivation
reduce SOD activity in the hippocampus and brainstem while the neocortex
showed no changes in association with either short-term or long-term
sleep deprivation. It has also been shown that 6 h sleep
deprivation increases antioxidants in the hippocampus, cerebellum, and
neocortex (Ramanathan et al. 2010).
Conversely, 96 h of sleep deprivation decreased antioxidants in the
hypothalamus, again, suggesting a delay in recovery from oxidative
stress after long periods of sleep deprivation (D’Almeida et al. 1998).
In our study, the hippocampus and prefrontal cortex both showed
increased TBARS values confirming that these structures are affected by
sleep deprivation and are important for memory. The reorganization of
human cerebral activity in hippocampus-neocortical networks after sleep
has recently been evaluated by functional magnetic resonance imaging
(Albouy et al. 2013). The interesting
study shows that sleep deprivation does not enhance but stabilizes
sleep-dependent motor sequence memory consolidation. Sleepers showed,
after retest, increased responses in the hippocampus and medial
prefrontal cortex while sleep-deprived subjects showed increased
responses in the putamen and cingulate cortex. Interestingly, it has
also been shown that the amygdala is critically involved in contextual
fear memory and this is also related to the cholinergic and
histaminergic systems (Bucherelli et al. 2006).
This is all important considering that motor sequence memory
consolidation is physiologically essential. Notably, chronic insomnia
has been recently associated with comorbidities and degenerative
disorders (Bruin et al. 2012; Miyata et al. 2013).
Also, animal experimentation has shown that the parkinsonian mouse
model presents increased levels of nitrite in the striatum secondary to
chronic exposure to paraquat (Yadav et al. 2013).
Our data indicates that the striatum, an important structure implicated
in both motor and memory function, is only affected by longer periods
of sleep deprivation.
An important aspect is to
understand how sleep deprivation increases oxidative stress in the
brain. Oxidative stress has been defined as a disturbance in the
equilibrium of prooxidants and antioxidants in favor of the former,
leading to potentially deleterious effects for lipids, proteins, DNA,
and RNA. These reactions can include fatty acid peroxidation of cellular
membranes, oxidation of sulfhydryl groups, and enzyme inactivation
(Brown and Naidoo 2010). The brain is
highly susceptible to oxidative stress due to several factors, namely,
high levels of polyunsaturated fatty acids, increased metabolic
activity, low antioxidant capacity, and the inability to repair neuronal
cells. If the antioxidants are not able to successfully clean radicals,
this will lead to oxidative damage to lipids resulting in oxidative
stress (Lobo et al. 2010).
Khadrawy et al. (2011)
demonstrated that 72 h of REM sleep deprivation increases the
production of NO in the rodent hippocampus. In the study, the authors
also reported that 72 h of REM sleep deprivation increased lipid
oxidation in both areas of the hippocampus and cortex (Khadrawy et al. 2011). Suer et al. (2011)
showed that 21 days of intermittent REM sleep deprivation
(recovery with 6 h of sleep each day) increased lipid oxidation and
decreased activity of SOD and GPx in rat hippocampus (Suer et al. 2011). Silva et al. (2004)
demonstrated that 72 h of sleep deprivation increased hippocampal
oxidized/reduced glutathione ratio as well as lipid peroxidation,
confirming an important role of hippocampal oxidative stress in memory
deficits (Silva et al. 2004).
Importantly, research has shown that an increase in NO release occurs
18 h after cessation of paradoxical sleep deprivation while a
reduction occurs 24 h after cessation of paradoxical sleep
deprivation (Clement et al. 2004).
The data presented in our study
show that lipid peroxidation (TBARS) increased in all sleep-deprived
groups and study areas. Notably, antioxidant activity, as measured by
nitrite levels, can modulate this parameter to promote a new redox state
of cells and combat the deleterious effects caused by ROS with the
possibility of reversing the stress oxidative process. Even with this
control, at some point after sleep deprivation, recovery periods may
prove inadequate, leading to elevated ROS and failure of the antioxidant
defense system to modulate this oxidative process. Thus, an increase in
TBARS levels, characterizing a situation of oxidative stress, is
observed.
Limitations of this study should
be acknowledged. Some antioxidants and protein synthesis inhibitors such
as protein kinase A were not measured where this data could have helped
clarify the process of sleep deprivation and memory. However, we
confirmed differential effects of sleep deprivation on fear conditioned
memory and oxidative stress, findings which may be of interest
particularly for posttraumatic stress disorder. Also, the multiple
platform method used in the present study is associated with less
anxiety than the single platform method. Nevertheless, it should be
noted that increased psychological stress and muscle fatigue still occur
under the multiple system and these should not be overlooked when
interpreting our data.
Conclusions
In the present study, we showed
that a shorter paradoxical sleep deprivation time is more beneficial to
avoid fear conditioning or posttraumatic stress memory. Also, the
striatum was found to be less vulnerable to oxidative stress induced by
paradoxical sleep deprivation. Compromise of the hippocampus and
prefrontal cortex confirmed a central role for these two structures in
working and aversive memory. We suggest that the variability and
lability of the observed behavior offers opportunities to manipulate
unwanted consolidated memory such as in the case of posttraumatic
stress.
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