Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level
Aging is believed to be a first-order risk factor for most neurodegenerative disorders. The neuronal cell loss that occurs with aging has been partly attributed to increased production of nitric oxide and high caspase activity. Melatonin (MLT) might have a role in the regulation of nitric oxide i...
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Інститут фізіології ім. О.О. Богомольця НАН України
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irk-123456789-1480952019-02-17T01:26:32Z Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level Akbulut, K.G. Guney, S. Akgun, H.N. Aktas, S.H. Akbulut, H. Cetin, F. Aging is believed to be a first-order risk factor for most neurodegenerative disorders. The neuronal cell loss that occurs with aging has been partly attributed to increased production of nitric oxide and high caspase activity. Melatonin (MLT) might have a role in the regulation of nitric oxide in the brain. We investigated the effects of MLT on the nitrite/nitrate levels and caspase-3 enzyme activity in the frontal cortex, temporal cortex, and hippocampus of young and aged rats. There was no significant difference between the nitrite levels in the frontal cortex and hippocampus of young and aged animals. In the temporal cortex of aged rats, the nitrite level, however, was significantly higher (P < 0.001). In the aged group, MLT significantly decreased these levels in the brain regions. Caspase-3 enzyme activity in the temporal and frontal cortices was significantly higher in aged rats when compared to the control group (P < 0.05). Melatonin did not cause significant changes in caspase-3 activity in any brain region of both young and aged rats. Thus, brain regions demonstrate different caspase-3 enzyme activities and nitrite levels in the aging process. Exogenous MLT administration might delay brain aging (by moderation of death of neurons and glia) via decreasing the nitrite level. В аспекті розвитку нейродегенеративних розладів старіння розглядається як фактор ризику першого порядку. Втрату нервових клітин, яка відбувається з віком, пов’язували, в усякому разі частково, зі збільшенням продукції оксиду азоту та високій активності каспаз. Мелатонін (МТ) може відігравати певну роль у регуляції рівня оксиду азоту в мозку. Ми досліджували впливи МТ на рівні нітритів/нитратів та ензиматичну активність каспази-3 у фронтальній і темпоральній корі та гіпокампі молодих і старих щурів. Істотних відмінностей між рівнями нітритів у фронтальній корі та гіпокампі молодих і старих тварин виявлено не було, проте цей рівень в темпоральній корі старих тварин був істотно вищим (P < 0.001). У групі старих щурів МТ істотно знижував рівні нітритів в структурах мозку. Активність каспази-3 у фронтальних і темпоральних зонах кори старих щурів була достовірно вище, ніж у контрольних тварин (P < 0.05). Мелатонін не викликав істотних змін активності каспази-3 у всіх досліджених структурах мозку як молодих, так і старих щурів. Отже, рівні активності каспази-3 та концентрації нітритів в різних структурах мозку в перебігу процесу старіння демонструють певну специфічність. Вплив екзогенного МТ, мабуть, затримує старіння мозку (зменшуючи інтенсивність загибелі нейронів і глії) за рахунок зниження рівнів нітриту 2013 Article Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level / K.G. Akbulut, S. Guney, F. Cetin, H.N. Akgun, S.H. Aktas, H. Akbulut // Нейрофизиология. — 2013. — Т. 45, № 3. — С. 215-220. — Бібліогр.: 39 назв. — англ. 0028-2561 http://dspace.nbuv.gov.ua/handle/123456789/148095 591.139:612.7:543.272.3 en Нейрофизиология Інститут фізіології ім. О.О. Богомольця НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| description |
Aging is believed to be a first-order risk factor for most neurodegenerative disorders. The
neuronal cell loss that occurs with aging has been partly attributed to increased production of
nitric oxide and high caspase activity. Melatonin (MLT) might have a role in the regulation
of nitric oxide in the brain. We investigated the effects of MLT on the nitrite/nitrate levels
and caspase-3 enzyme activity in the frontal cortex, temporal cortex, and hippocampus of
young and aged rats. There was no significant difference between the nitrite levels in the
frontal cortex and hippocampus of young and aged animals. In the temporal cortex of aged
rats, the nitrite level, however, was significantly higher (P < 0.001). In the aged group,
MLT significantly decreased these levels in the brain regions. Caspase-3 enzyme activity
in the temporal and frontal cortices was significantly higher in aged rats when compared
to the control group (P < 0.05). Melatonin did not cause significant changes in caspase-3
activity in any brain region of both young and aged rats. Thus, brain regions demonstrate
different caspase-3 enzyme activities and nitrite levels in the aging process. Exogenous MLT
administration might delay brain aging (by moderation of death of neurons and glia) via
decreasing the nitrite level. |
| format |
Article |
| author |
Akbulut, K.G. Guney, S. Akgun, H.N. Aktas, S.H. Akbulut, H. Cetin, F. |
| spellingShingle |
Akbulut, K.G. Guney, S. Akgun, H.N. Aktas, S.H. Akbulut, H. Cetin, F. Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level Нейрофизиология |
| author_facet |
Akbulut, K.G. Guney, S. Akgun, H.N. Aktas, S.H. Akbulut, H. Cetin, F. |
| author_sort |
Akbulut, K.G. |
| title |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level |
| title_short |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level |
| title_full |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level |
| title_fullStr |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level |
| title_full_unstemmed |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level |
| title_sort |
melatonin delays brain aging by decreasing the nitric oxide level |
| publisher |
Інститут фізіології ім. О.О. Богомольця НАН України |
| publishDate |
2013 |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/148095 |
| citation_txt |
Melatonin Delays Brain Aging by Decreasing the Nitric Oxide Level / K.G. Akbulut, S. Guney, F. Cetin, H.N. Akgun, S.H. Aktas, H. Akbulut // Нейрофизиология. — 2013. — Т. 45, № 3. — С. 215-220. — Бібліогр.: 39 назв. — англ. |
| series |
Нейрофизиология |
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2025-07-12T18:18:53Z |
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| fulltext |
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 3 215
UDC 591.139:612.7:543.272.3
K. G. AKBULUT1, S. GUNEY1, F. CETIN1, H. N. AKGUN2,
S. H. AKTAS2, and H. AKBULUT2
MELATONIN DELAYS BRAIN AGING BY DECREASING
THE NITRIC OXIDE LEVEL
Received November 12, 2012.
Aging is believed to be a first-order risk factor for most neurodegenerative disorders. The
neuronal cell loss that occurs with aging has been partly attributed to increased production of
nitric oxide and high caspase activity. Melatonin (MLT) might have a role in the regulation
of nitric oxide in the brain. We investigated the effects of MLT on the nitrite/nitrate levels
and caspase-3 enzyme activity in the frontal cortex, temporal cortex, and hippocampus of
young and aged rats. There was no significant difference between the nitrite levels in the
frontal cortex and hippocampus of young and aged animals. In the temporal cortex of aged
rats, the nitrite level, however, was significantly higher (P < 0.001). In the aged group,
MLT significantly decreased these levels in the brain regions. Caspase-3 enzyme activity
in the temporal and frontal cortices was significantly higher in aged rats when compared
to the control group (P < 0.05). Melatonin did not cause significant changes in caspase-3
activity in any brain region of both young and aged rats. Thus, brain regions demonstrate
different caspase-3 enzyme activities and nitrite levels in the aging process. Exogenous MLT
administration might delay brain aging (by moderation of death of neurons and glia) via
decreasing the nitrite level.
Keywords: aging, caspase-3, melatonin, nitric oxide, temporal cortex, frontal cortex,
hippocampus.
1 Gazi University School of Medicine, Department of Physiology, Ankara,
Turkey.
2 Ankara University School of Medicine, Department of Medical Oncology,
Ankara, Turkey.
Correspondence should be addressed to
K. G. Akbulut (e-mail: kgakbulut@yahoo.com),
S. Guney (e-mail: sguney@gazi.edu.tr),
F. Cetin (e-mail: ferihan.cetin@izmir.edu.tr),
H. N. Akgun (e-mail: akgun.hnalan@hotmail.com),
S. H. Aktas (e-mail: handeenfez@yahoo.com), or
H. Akbulut (e-mail: akbulut@medicine.ankara.edu.tr).
INTRODUCTION
Aging is one of the risk factors for the neurodegenerative
diseases [1]. Recently, it was reported that aging
is accompanied by the development of some
inflammatory processes at the tissue level in different
parts of the body and in the brain in particular [2].
Aging intemsifies the glial cell activity in the brain
[3], and the number of abnormal astrocytes increases
with aging [4]. The increased apoptotic cell death of
astrocytes observed in neurodegenerative diseases,
such as Alzheimer’s disease, is consistent with these
findings [5]. Likewise, increased activity of caspase-3
and caspase-9 involved in the process of apoptosis
has been reported in neurodegenerative disorders, like
Alzheimer’s, Parkinson’s, and Huntington’s disease
[6, 7].
The existence of nitric oxide synthase (NOS)-
containing neurons in the cerebral cortex, cerebellum,
hippocampus, and hypothalamus suggests a possible
role of nitric oxide (NO) in the oxidative-antioxidative
processes, apoptosis, and aging of the brain
[8, 9]. Nitric oxide can behave either as a free-radical
precursor or an antioxidant and neuroprotective agent
[10]. Depending on its local concentration and cell
type, NO can be an agent promoting either apoptosis
or cell survival. Inhibition/induction of apoptosis by
NO is mediated by downstream caspases, including
caspase-3 [11].
Reactive oxygen and nitrogen species (ROSs and
RONs), potent inducers of oxidative damage, have
been shown to trigger apoptosis [12]. Accordingly,
antioxidant treatment was shown to decrease the
rate of this process [13]. Superoxide and hydroxyl
radicals and NO might also be related to aging and, in
particular, aging-related loss of cognitive functions in
humans [14].
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 3216
K. G. AKBULUT, S. GUNEY, F. CETIN et al.
Melatonin (MLT) demonstrates a wide range of
actions in different parts of the body, including
effects on the circadian rhythm and neuroendocrine
or immune functions [15-17]. Melatonin and its
metabolites are potent radical scavengers protecting
cells from damage induced by a variety of oxidants,
including hydroxyl radicals and lipid peroxidation
products [18, 19]. Melatonin was also reported to
suppress increased caspase activity in the liver in a rat
aging model [20]. Likewise, it was shown that MLT
prevents spontaneous neuronal apoptosis by inhibiting
downstream targets of Akt, GSK3b, and FOXO-1 [15].
In our study, we aimed to investigate changes in the
nitrate levels and caspase-3 activity in different brain
regions of young and aged rats and the effects of MLT
on these parameters.
METHODS
Animal Groups and Tissue Homogenization. A
total of 43 young (4-month-old) and aged (14-month-
old) male Wistar albino rats was used in this study.
The rats were divided into the control group
(10 animals in the young subgroup and 10 ones in the
aged one) and the melatonin group (10 animals in the
young subgroup and 13 ones in the aged subgroup).
While rats of the control group were given 0.1 ml of
phosphate-buffered saline containing 1% ethanol, the
others (melatonin group) were injected subcutaneously
with MLT (Sigma SM 5250, USA) at a dose of 10 mg/kg
per day dissolved in 0.1 ml of phosphate-buffered
saline containing 1% ethanol for 7 days. A maximum
of four animals were kept per cage, under conditions
of equal periods of light and dark (12/12 h) in a
room with lighting control (lights on at 08.00 and off
at 20.00). Injections were given daily at 18.00, 2 h
before the light was switched off, to compensate a
presumed hormone deficiency in aged animals. On
the 7th day of the experiment, the rats were sacrificed
at 10.00, and brain tissues were removed and dissected
on ice. Tissue samples from the frontal cortex, temporal
cortex, and hippocampus were kept in a liquid nitrogen
tank until analysis.
The samples were then homogenized in 200 μl
of a cell lysis buffer (Promega, USA) using a tissue
homogenizer (Heidolph Diax 900, Germany). The
homogenate was centrifuged at 16,000 rpm for
15 min at 4°C, and protein concentrations in the
cleared extracts were measured prior to storage at
–86°C. Cleared extracts of the tissue homogenates
were assayed for caspase-3 activity.
Measurement of Caspase-3 Activity. In this
study, we used the estimates of caspase-3 activity
as an indicator of caspase-dependent apoptosis. The
caspase-3 activity was determined by a colorimetric
assay kit (Promega, USA) using acetyl-Asp-Glu-Val-
Asp-p-nitroanilide (pNA) as the substrate. From 25
to 100 μg of total protein of the clear extracts of brain
tissue were used for the assay. The specific caspase
activity was expressed as picomoles yielding pNA
per microgram of protein of the supernatant of tissue
homogenates [21].
Measurement of the Total Nitrite Levels in the
Brain Regions. The nitrite levels were measured
using an enzyme-linked immunosorbent assay reader
by vanadium chloride (VCl3)/Griess assay. Prior to
nitrite determination, tissues were homogenized in
five volumes of phosphate-buffered saline (pH = 7.5)
and centrifuged at 2,000g for 5 min. Then, 0.25 ml of
0.3 N NaOH was added to 0.5 ml of the supernatant.
After incubation for 5 min at room temperature,
0.25 ml of 5% (w/v) ZnSO4 was added for
deproteinization. This mixture was then centrifuged at
3,000g for 20 min, and supernatants were used for the
assays [22].
Statistical Analysis. Differences among the
results obtained in the test groups were compared
by one-way ANOVA and the Mann–Whitney U test.
The Spearman’s test was used for nonparametric
correlation analysis. Differences with two-sided
P < 0.05 were considered to be significant.
RESULTS
Exogenous MLT Decreases the Nitrite Level in the
Cerebral Cortex. There were significant differences
between the nitrite levels in different brain regions
of young and aged rats. The nitrite level in the
frontal cortex was significantly higher than that in
the temporal cortex and hippocampus of young rats
(P = 0.014 and P < 0.001, respectively). Likewise,
the nitrite levels in the cortical regions (frontal and
temporal cortices) in the aged group were higher
than those in the hippocampus (P = 0.043 and P <
0.001, respectively). No significant differences in
the above levels were found in the frontal cortex and
hippocampal region with respect to age. However, the
nitrite level in the temporal cortex was significantly
higher compared to that in the young one (P < 0.001)
(Fig. 1, Table 1).
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 3 217
MELATONIN DELAYS BRAIN AGING BY DECREASING THE NO LEVEL
were close to each other in young rats (Fig. 2,
Table 2). Though not significant, the enzyme activity
in the frontal cortex was the lowest among the
studied brain regions in the young group. However,
the caspase-3 activity in the temporal cortex was
significantly higher than that in the frontal cortex and
hippocampus in the aged group (P = 0.05 and P = 0.03,
respectively; Fig. 2).
The age-related increase in caspase-3 activity in
80
1
2
1
2
1
2
***
mM
Frontal cortex HippocampusTemporal cortex
70
60
50
40
30
20
10
0
Fig. 1. Nitrite/nitrate levels in different brain regions of control
(untreated) groups of young (1) and aged (2) rats. *** Significant
difference with P < 0.001.
Рис. 1. Рівні нітритів/нітратів в різних ділянках мозку контроль-
них молодих (1) та старих (2) щурів.
30
25
20
10
5
0
15
pmol/mg protein
10
1010
***
1
2
1
1
2
2**
Fig. 2. Caspase-3 activity in сontrol young (1) and aged (2) rats.
**Significant difference with P = 0.010; *** the same with P < 0.002.
Рис. 2. Активність каспази-3 в різних ділянках мозку контроль-
них молодих (1) та старих (2) щурів.
Frontal cortex HippocampusTemporal cortex
TABLE 1. Nitrite/Nitrate Levels (µM) in Different Brain Regions of Assigned Rat Groups
Т а б л и ц я 1. Рівні нітратів/нітритів (мкМ) у різних ділянках мозку щурів досліджених груп
Brain regions
Young rats P Aged rats P
control melatonin control melatonin
Frontal cortex 52.7 ± 5.3 45.0 ± 3.8 0.323 50.4 ± 11.3 15.3 ± 2.9 <0.001
Temporal cortex 33.2 ± 3.0 23.0 ± 3.2 0.221 67.5 ± 3.9 30.8 ± 6.1 <0.001
Hippocampus 25.6 ± 4.2 15.0 ± 2.2 0.152 33.3 ± 8.3 22.1 ± 2.9 0.116
Footnote. Means ± s.e.m. are shown.
TABLE 2. Caspase-3 Activity (pmol/μg protein) in Different Brain Regions of Assigned Rat Groups
Т а б л и ц я 2. Активність каспази-3 (пмоль/мкг протеїну) у різних ділянках мозку щурів досліджених груп
Brain regions
Young P Aged P
control melatonin control melatonin
Frontal cortex 1.2 ± 1.1 3.6 ± 2.1 0.620 14.4 ± 2.2 12.8 ± 0.9 0.764
Temporal cortex 6.3 ± 3.8 7.1 ± 2.8 0.877 25.4 ± 1.6 26.6 ± 5.9 0.829
Hippocampus 4.96 ± 2.7 5.7 ± 2.5 0.866 8.3 ± 3.2 4.9 ± 1.1 0.465
Footnote. Means ± s.e.m. are shown.
Exogenous MLT caused insignificant decreases
in the nitrite levels in young rats. Short-term MLT
treatment significantly decreased the nitrite level
in cortical regions of aged rats, while a decrease in
the hippo campus was noticeable but not significant
(Table 1).
Exogenous MLT and Caspase Activity in the
Brain. We found that the levels of caspase-3 activity in
the frontal cortex, temporal cortex, and hippocampus
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 3218
K. G. AKBULUT, S. GUNEY, F. CETIN et al.
the frontal cortex was more prominent than that in
the temporal cortex (> 10 times and about 4 times,
respectively). There was also a slight insignificant
increase in the caspase-3 activity in the hippocampus
with aging (Table 2, Fig.2).
Short-term treatment with exogenous MLT caused
no significant changes in caspase-3 activity within
different brain regions. Likewise, no significant
change in the levels of caspase-3 activity in the cortical
regions and hippocampus of the aged group was found
after such treatment (Table 2).
The relationship between nitrite levels and caspase-3
activity was different in the control groups of young
and aged rats. While there was a considerable, though
statistically insignificant (r = –0.398; P = 0.083), trend
toward negative correlation between the nitrite and
caspase-3 activity in the young group, the analogous
correlation was positive in the aged group (r = 0.315;
P = 0.253).
DISCUSSION
There is an increased incidence of abnormal astrocytes
during aging. Agents such as IL-1 and NO produced by
those abnormal astrocytes could be partly responsible
for general neuronal cell loss [23]. The microglial
cell activity is increased in both neurodegenerative
diseases and aging [24]. Reactive glial cells may
intensify the oxidative damage in the brain. Activated
glial cells lead to a more intense formation of ROSs,
NO, and peroxynitrite-derived radicals [25]. Oxidative
stress induces cognitive and motor deterioration by
initiating inflammatory processes in the brain during
aging [26]. Siles et al. [27] reported that different
NOS activities in the cerebral cortex and cerebellum
are age-dependent.
The reports on the level of NO and NOS activity
during aging are contradictory [28-30]. Liu et al. [30]
found that an increased eNOS activity was observed
in the hippocampus and dentate gyrus with aging,
but changes in the areas CA1 and CA3 were mild.
Likewise, Blanco et al. [31] observed no age-related
difference in the nitrite level in the cerebellum. In our
study, we found that the nitrite level in the temporal
cortex increases with aging, but this was not the case
in the frontal cortex and hippocampus (Fig. 2). The
microglial activity in the temporal lobe was reported
to increase with aging, which is associated with
neuronal loss in the temporal cortex and a cognitive
function decrease [32, 33]. Accordingly, an increased
pro-oxidant cytokine production in mouse brain tissues
induced by lipopolysaccharides was found during
aging [34].
Melatonin, the chief secretory product of the
epiphysis (pineal gland) is an efficient free-radical
scavenger in the body and brain. By preventing
oxidative damage, MLT reduces the intensity of
apoptosis of neurons and glial cells [35]. In our
experiments, we found that short-term exogenous MLT
treatment significantly decreases the nitrite levels in
the cortical regions but not in the hippocampus of aged
rats (Table 1).
Increased apoptosis in various tissues of the body
is one of the hallmarks of the aging process. Earlier,
we and others found that caspase activity in the liver,
lungs, spleen, and gastric mucosa increased with
aging [36, 37]. As well, increased caspase-3 activity
in cortical regions of the brain during aging was
shown previously [38]. The caspase-3 activity in the
hippocampus was reported to increase significantly
in old individuals when compared to that in young
ones [23]. We, however, could not find a significant
increase in the caspase-3 activity in the hippocampus
with aging (Table 2). Instead, we found significant
increases in the enzyme activity in the cerebral
cortices in the current study.
Melatonin has been shown to inhibit caspase-3
activity and JNK-mediated cell death of neurons
induced by the action of a neurotoxin [39]. We showed
earlier that 1-week-long treatment with MLT decreased
the caspase-3 level in the gastrointestinal system
[36]. In our study, however, we found that short-term
(1 week) introduction of exogenous MLT exerted no
significant effect on the increased caspase-3 activity in
the brain regions of aged rats. The discordance of the
effects of MLT on nitrite levels and caspase-3 activity
in the brain might be related to the short-term action of
the drug (1 week). Therefore, testing of the effects of
prolonged administration of MLT on caspase activity
in brain tissues would be a subject of another study.
Our results suggest that exogenous MLT provides
effective free-radical scavenging in the cerebral cortex
of rats. One-week-long MLT treatment, however,
seems insufficient to decrease neuronal or glial
apoptosis mediated by caspase-3.
The study was carried out in accordance with the internationly
accepted ethical principles.
The authors, K. G. Akbulut, S. Guney, F. Cetin, H. N. Akgun,
S. H. Aktas, and H. Akbulut, declare that there is no conflict of interests
among them.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 3 219
MELATONIN DELAYS BRAIN AGING BY DECREASING THE NO LEVEL
К. Г. Акбулут1, С. Гуней1, Ф. Цетін1, Х. Н. Акгун2,
С. Х. Акташ2, Х. Акбулут2
МЕЛАТОНІН ЗАТРИМУЄ СТАРІННЯ МОЗКУ
ЗА РАХУНОК ЗНИЖЕННЯ РІВНЯ ОКСИДУ АЗОТУ
1 Медичний університет Гази (відділ фізіології), Анкара
(Туреччина).
2 Медичний університет Анкари (відділ медичної
онкології), Анкара (Туреччина).
Р е з ю м е
В аспекті розвитку нейродегенеративних розладів старіння
розглядається як фактор ризику першого порядку. Втрату не-
рвових клітин, яка відбувається з віком, пов’язували, в уся-
кому разі частково, зі збільшенням продукції оксиду азоту
та високій активності каспаз. Мелатонін (МТ) може відігра-
вати певну роль у регуляції рівня оксиду азоту в мозку. Ми
досліджували впливи МТ на рівні нітритів/нитратів та ензи-
матичну активність каспази-3 у фронтальній і темпоральній
корі та гіпокампі молодих і старих щурів. Істотних відмін-
ностей між рівнями нітритів у фронтальній корі та гіпокам-
пі молодих і старих тварин виявлено не було, проте цей рі-
вень в темпоральній корі старих тварин був істотно вищим
(P < 0.001). У групі старих щурів МТ істотно знижував рівні
нітритів в структурах мозку. Активність каспази-3 у фрон-
тальних і темпоральних зонах кори старих щурів була до-
стовірно вище, ніж у контрольних тварин (P < 0.05). Мела-
тонін не викликав істотних змін активності каспази-3 у всіх
досліджених структурах мозку як молодих, так і старих щу-
рів. Отже, рівні активності каспази-3 та концентрації нітри-
тів в різних структурах мозку в перебігу процесу старіння
демонструють певну специфічність. Вплив екзогенного МТ,
мабуть, затримує старіння мозку (зменшуючи інтенсивність
загибелі нейронів і глії) за рахунок зниження рівнів нітриту.
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