Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy
Scorpion venom is a traditional antiepileptic medicine in Asia. We examined the effects of scorpion venom heat-resistant protein (SVHRP) on seizure behavior of rats with kainate-induced epilepsy and expression of proenkephalin (pENK) in their hippocampus. Subcutaneous injections of convulsive dos...
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Інститут фізіології ім. О.О. Богомольця НАН України
2013
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Sun, Y. Cui, X. Yin, Sh Yu, D. Li, Sh. Zhang, W. Zhao, J. 2019-02-17T09:43:18Z 2019-02-17T09:43:18Z 2013 Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy / Y. Sun, X. Cui, Sh. Yin, D. Yu, Sh. Li, W. Zhang, J. Zhao // Нейрофизиология. — 2013. — Т. 45, № 4. — С. 358-361. — Бібліогр.: 11 назв. — англ. 0028-2561 https://nasplib.isofts.kiev.ua/handle/123456789/148124 616.853+616.8 Scorpion venom is a traditional antiepileptic medicine in Asia. We examined the effects of scorpion venom heat-resistant protein (SVHRP) on seizure behavior of rats with kainate-induced epilepsy and expression of proenkephalin (pENK) in their hippocampus. Subcutaneous injections of convulsive doses of kainic acid (KA, 10 mg/kg) evoked acute epileptic seizures; the intensity of such seizures was measured after subsequent injections of lower (subthreshold in the norm) doses of KA (5 mg/kg). Scorpion venom heat-resistant protein in a dose of 125 mg/kg was given in a part of the animals through i.p. injections daily during 10 days; rats of the control groups were injected with normal saline. Behavioral indices were measured, and the hippocampus was taken for pENK mRNA estimation by RTPCR analysis. The mean behavioral score of seizure sensitivity in the SVHRP-treated group was smaller significantly (P < 0.05) compared to that in the control group (1.19 vs 2.93). The pENK mRNA level was dramatically greater in hippocampal neurons of KA-treated rats with a high seizure sensitivity, while in the SVHRP-treated group the respective index was significantly lower. Thus, SVHRP inhibits behavior seizures in epilepsy and reverses the abnormally increased pENK mRNA in hippocampal neurons of such animals Отрута скорпіона є традиційним антиепілептичним терапевтичним засобом в Азії. Ми вивчали вплив термостійкого протеїну з отрути скорпіона (ТСПОС) на судорожну поведінку щурів з викликаною каїнатом епілепсією та на експресію проенкефаліну (пEНК) у їх гіпокампі. Підшкірні ін’єкції «конвульсивних» доз каїнової кислоти (КК, 10 мг/кг) призводили до розвитку гострих епілептичних судом; інтенсивність таких судом вимірювали після наступних ін’єкцій КК (5 мг/кг, підпорогова доза в нормі). Частина тварин отримувала ТСПОС у дозі 125 мкг/кг шляхом внутрішньоочеревинних ін’єкцій щоденно протягом 10 днів; щурам контрольної групи вводили фізіологічний розчин. Вимірювали поведінкові показники; гіпокамп ізолювали для подальшої оцінки пEНК мРНК з використанням RT-PCR-аналізу. Усереднені поведінкові показники судомної чутливості в групі тварин, котрі отримували ТСПОС, були істотно нижче (P < 0.05) таких у контрольній групі (1.19 проти 2.93). У нейронах гіпокампа щурів із високою судомною чутливістю, котрі отримували КК, рівень пЕНК мРНК був істотно вищим, тоді як у тварин з ін’єкціями ТСПОС відповідний показник був значно нижчим. Отже, ТСПОС гальмує поведінкові судоми при епілепсії та різко зменшує аномально збільшений рівень пEНК мРНК у нейронах гіпокампа таких тварин. This work was supported by grants from the National Natural Science Foundation of China, No. 31171037/c090202, the Liaoning Province Education Department Scientific Technological Research, LS2010057, and the Doctoral Fund of the Ministry of Education of China for Youth Scholars (20092105120006). en Інститут фізіології ім. О.О. Богомольця НАН України Нейрофизиология Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy Вплив термостійкого протеїну з отрути скорпіона на судорожну поведінку та експресію проенкефаліну у щурів з викликаною каїнатом епілепсією Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy |
| spellingShingle |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy Sun, Y. Cui, X. Yin, Sh Yu, D. Li, Sh. Zhang, W. Zhao, J. |
| title_short |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy |
| title_full |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy |
| title_fullStr |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy |
| title_full_unstemmed |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy |
| title_sort |
effects of scorpion venom heat-resistant protein on seizure behavior and expression of proenkephalin in rats with kainate-induced epilepsy |
| author |
Sun, Y. Cui, X. Yin, Sh Yu, D. Li, Sh. Zhang, W. Zhao, J. |
| author_facet |
Sun, Y. Cui, X. Yin, Sh Yu, D. Li, Sh. Zhang, W. Zhao, J. |
| publishDate |
2013 |
| language |
English |
| container_title |
Нейрофизиология |
| publisher |
Інститут фізіології ім. О.О. Богомольця НАН України |
| format |
Article |
| title_alt |
Вплив термостійкого протеїну з отрути скорпіона на судорожну поведінку та експресію проенкефаліну у щурів з викликаною каїнатом епілепсією |
| description |
Scorpion venom is a traditional antiepileptic medicine in Asia. We examined the effects
of scorpion venom heat-resistant protein (SVHRP) on seizure behavior of rats with
kainate-induced epilepsy and expression of proenkephalin (pENK) in their hippocampus.
Subcutaneous injections of convulsive doses of kainic acid (KA, 10 mg/kg) evoked acute
epileptic seizures; the intensity of such seizures was measured after subsequent injections
of lower (subthreshold in the norm) doses of KA (5 mg/kg). Scorpion venom heat-resistant
protein in a dose of 125 mg/kg was given in a part of the animals through i.p. injections
daily during 10 days; rats of the control groups were injected with normal saline. Behavioral
indices were measured, and the hippocampus was taken for pENK mRNA estimation by RTPCR analysis. The mean behavioral score of seizure sensitivity in the SVHRP-treated group
was smaller significantly (P < 0.05) compared to that in the control group (1.19 vs 2.93).
The pENK mRNA level was dramatically greater in hippocampal neurons of KA-treated rats
with a high seizure sensitivity, while in the SVHRP-treated group the respective index was
significantly lower. Thus, SVHRP inhibits behavior seizures in epilepsy and reverses the
abnormally increased pENK mRNA in hippocampal neurons of such animals
Отрута скорпіона є традиційним антиепілептичним терапевтичним засобом в Азії. Ми вивчали вплив термостійкого
протеїну з отрути скорпіона (ТСПОС) на судорожну поведінку щурів з викликаною каїнатом епілепсією та на експресію проенкефаліну (пEНК) у їх гіпокампі. Підшкірні ін’єкції
«конвульсивних» доз каїнової кислоти (КК, 10 мг/кг) призводили до розвитку гострих епілептичних судом; інтенсивність таких судом вимірювали після наступних ін’єкцій КК
(5 мг/кг, підпорогова доза в нормі). Частина тварин отримувала ТСПОС у дозі 125 мкг/кг шляхом внутрішньоочеревинних ін’єкцій щоденно протягом 10 днів; щурам контрольної групи вводили фізіологічний розчин. Вимірювали
поведінкові показники; гіпокамп ізолювали для подальшої
оцінки пEНК мРНК з використанням RT-PCR-аналізу. Усереднені поведінкові показники судомної чутливості в групі
тварин, котрі отримували ТСПОС, були істотно нижче (P < 0.05) таких у контрольній групі (1.19 проти 2.93). У нейронах гіпокампа щурів із високою судомною чутливістю,
котрі отримували КК, рівень пЕНК мРНК був істотно вищим, тоді як у тварин з ін’єкціями ТСПОС відповідний показник був значно нижчим. Отже, ТСПОС гальмує поведінкові судоми при епілепсії та різко зменшує аномально
збільшений рівень пEНК мРНК у нейронах гіпокампа таких тварин.
|
| issn |
0028-2561 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/148124 |
| citation_txt |
Effects of Scorpion Venom Heat-Resistant Protein on Seizure Behavior and Expression of Proenkephalin in Rats with Kainate-Induced Epilepsy / Y. Sun, X. Cui, Sh. Yin, D. Yu, Sh. Li, W. Zhang, J. Zhao // Нейрофизиология. — 2013. — Т. 45, № 4. — С. 358-361. — Бібліогр.: 11 назв. — англ. |
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NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 4358
UDC 616.853+616.8
Y. SUN1, X. CUI2, Sh. YIN3, D. YU3, Sh. LI4, W. ZHANG3, and J. ZHAO3
EFFECTS OF SCORPION VENOM HEAT-RESISTANT PROTEIN ON SEIZURE
BEHAVIOR AND EXPRESSION OF PROENKEPHALIN IN RATS WITH KAINATE-
INDUCED EPILEPSY
Received November 22, 2012.
Scorpion venom is a traditional antiepileptic medicine in Asia. We examined the effects
of scorpion venom heat-resistant protein (SVHRP) on seizure behavior of rats with
kainate-induced epilepsy and expression of proenkephalin (pENK) in their hippocampus.
Subcutaneous injections of convulsive doses of kainic acid (KA, 10 mg/kg) evoked acute
epileptic seizures; the intensity of such seizures was measured after subsequent injections
of lower (subthreshold in the norm) doses of KA (5 mg/kg). Scorpion venom heat-resistant
protein in a dose of 125 mg/kg was given in a part of the animals through i.p. injections
daily during 10 days; rats of the control groups were injected with normal saline. Behavioral
indices were measured, and the hippocampus was taken for pENK mRNA estimation by RT-
PCR analysis. The mean behavioral score of seizure sensitivity in the SVHRP-treated group
was smaller significantly (P < 0.05) compared to that in the control group (1.19 vs 2.93).
The pENK mRNA level was dramatically greater in hippocampal neurons of KA-treated rats
with a high seizure sensitivity, while in the SVHRP-treated group the respective index was
significantly lower. Thus, SVHRP inhibits behavior seizures in epilepsy and reverses the
abnormally increased pENK mRNA in hippocampal neurons of such animals.
Keywords: scorpion venom heat-resistant protein, proenkephalin, kainate-induced
epilepsy.
1 Functional Lab, Dalian Medical University, Dalian, China.
2 Seven-year-program medical student, Dalian Medical University, Dalian,
China.
3 Department of Physiology, Dalian Medical University, Dalian, China.
4 Medical postgraduate student, Dalian Medical University, Dalian, China.
Correspondence should be addressed to Jie Zhao
(e-mail: dlyipingsun@163.com)
INTRODUCTION
Epilepsy is a widespread neurodegenerative disease;
it can become a stubborn and intractable disease
in clinics due to the formation of abnormally high
epilepsy sensitivity. It was shown that opioid peptides
may be significantly involved in the mechanisms of
underlying formation of epilepsy sensitivity. The
content of enkephalin (ENK) is the highest among
opioid peptides expressed widely in the brain.
Scorpion venom is a traditional antiepileptic
medicine in Asia, and scorpion venom heat-resistant
protein (SVHRP) extracted via a special process is the
major component having antiepileptic activity.
In this study, we explored the effects of SVHRP on
seizure behavior of rats with experimentally induced
epilepsy and expression of proenkephalin (pENK) in
their hippocampus.
METHODS
Experimental Materials and Grouping. Healthy
male Sprague-Dawley rats weighing 180 to 220 g
were obtained from the Experimental Animal Center
of the Dalian Medical University. Scorpion venom
was collected from the Buthus martensii Karsch
through a special process developed in Yiyang Town,
Henan Province, China (National Invention Patent No.
ZL01106166.9). Scorpion venom heat-resistant protein
was partially purified using an ultrafilter. Kainate
(kainic acid, KA) was purchased from Sigma (USA);
RT-PCR kit, PCR primers, and internal standards were
from Takara Biotechnology Co. Ltd. (Dalian, China).
All tested animals were randomly divided into two
groups. Subcutaneous injections of KA in a convulsive
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 4 359
EFFECTS OF SCORPION VENOM HEAT-RESISTANT PROTEIN
dose (10 mg/kg) were conducted to induce acute
epileptic seizures; animals of another group were
injected with equal volumes of normal saline (NS).
Normal saline and SVHRP (125 mg/kg) were given
for two groups of rats through i.p. injections daily
for a period of 10 days. Subcutaneous injections of
a subthreshold (in the norm) dose of KA (5 mg/kg)
or saline were then given in these two groups.
Thus, four groups of animals were formed, (i)
model group (KA+NS+0.5KA), (ii) therapy group
(KA+SVHRP+0.5KA), (iii) blank control group
(NS+NS+0.5NS), and (iv) negative control group
(NS+SVHRP+0.5NS). The epilepsy susceptibility
was measured in these groups according to the seizure
score.
Behavior Examination. The seizures were scored
using a modified Racine scale. Chewing, head
nodding, unilateral forelimb clonus, rearing with
bilateral forelimb clonus, and rearing with bilateral
forelimb clonus and falling back were recorded as
grades 1 to 5, respectively.
Proenkephalin mRNA by RT-PCR Analysis.
Reverse transcription was conducted after the
extraction of total RNA. The reaction mix at a total
volume of 20 ml included 2.0 ml 10×RNA PCR buffer,
2.0 ml dNTP mixture, 0.5 ml RNase inhibitor, 1.0 ml
AMV reverse transcriptase, 8.5 ml RNase-free dH2O,
1.0 ml (= 1mg) of RNA samples, 1.0 ml random primer,
and 4.0 ml MgC12. Reaction conditions were the
following: +30°C for 10 min, +42°C for 60 min, +99°C
for 5 min, and +5°C for 5 min. PCR amplification: the
cDNA was used as a formwork for PCR amplification
in a total volume of 25 ml, including 2.0 ml 10×RNA
PCR buffer, 14.875 ml RNase-free dH2O, 0.125 ml
Taq DNA polymerase, 5.0 ml reverse transcription
product, 0.75 ml of 40 mM L-1 3´5 primer, 0.75 ml of
40 mM L-1 3´ primer, and 1.5 ml MgC12. Reaction
conditions were the following: +94°C for 45 sec,
+60°C for 45 sec, and 72°C for 45 sec by 31 cycles;
terminal extension +72°C for 5 min; 1.5% agarose
gel electrophoresis was used for testing PCR products.
Quantitative analysis of the average absorbance of
PCR products was measured by a gel analysis system;
statistical analysis was carried out using standard
software. The primer sequence was the following:
pENK f 5′-GTCCACCATTGGTTCAGAAGG -3′;
r 5′-ACCGCATAAAGCCTCCGTATC-3′.
RESULTS
Seizure Susceptibility Testing. In the model
(KA+NS+0.5KA) group, 11 rats developed seizures at
grade 3 or above, and one animal developed grade 2.
In 12 rats of the therapy (KA+SVHRP+0.5KA) group,
two animals showed grade 3 or above, three animals
showed grade 2, two rats showed grade 1, and the
remaining five showed only occasional chewing or
no seizures. Thus, the seizure susceptibility behavior
score in the therapy group was significantly lower
(P < 0.05) than that in the model group: the mean
score in the therapy group corresponded only to 40.0%
of the respective index in the model group (Fig. 1).
RT-PCR Results of pENK mRNA. Kainic acid-
treated rats with a high seizure sensitivity showed
strongly upregulated pENK mRNA in hippocampal
neurons compared with the other three groups, and
differences were statistically significant (P < 0.01).
The expression of pENK mRNA in hippocampal
neurons of rats of the therapy group was significantly
lower (P < 0.05) than that in the control group
(Figs. 2 and 3).
DISCUSSION
Epilepsy is one of the most widespread neurological
disorders. In adults with temporal lobe epilepsy
(TLE), complex partial seizures have the poorest
0,5
0
KA+NS+0,5KA KA+SVHRP+0,5KA
1,0
1
2
1,5
2,0
2,5
3,0
3,5
*
F i g. 1. Mean seizure susceptibility behavior scores (vertical scale)
of kainic acid (KA)-treated rats. 1 and 2) Model (KA+NS+0.5KA)
and therapy (KA+SVHRP+0.5KA) groups, respectively. *P < 0.05
vs the model group.
Р и с. 1. Середні оцінки (поведінкові бали) судомної чутливості
(вертикальна шкала) у щурів, котрі отримували каїнову кислоту.
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 4360
Y. SUN, X. CUI, Sh. YIN et al.
dose of KA result in the development of the limbic
status epilepticus with a high seizure susceptibility
[1]. Therefore, the KA-induced epilepsy model has
been widely used to study human TLE [2].
Enkephalin (ENK) is one of the important endo-
genous opioid peptides first isolated in 1975 [3].
Hong first proved by radioimmunoassay that the
content of ENK in the hippocampus increases after
treatment with the lowest dose of KA inducing acute
seizures [4, 5]. Later on, several studies suggested
that the expression of ENK and its precursor pENK
mRNA in the hippocampus demonstrate rather high
values in a variety of different types of animal models
of TLE, including the KA model [2, 6], penicillin-
induced epilepsy model, model based on electric-
light or chemical kindling, that based on electrical
stimulation of the hippocampal perforant pathway,
and other animal models [7, 8]. The discharges and
seizures in abnormal EEGs were detected after
intracerebroventricular injections of ENK. In addition,
the ENK levels in the cerebrospinal fluid of epilepsy
patients were also found to be increased significantly
[9, 10]. A few studies indicated that ENK is also
involved in the formation of high epilepsy sensitivity,
and long-lasting expression of pENK mRNA was
observed in the hippocampus of susceptible animals
with epileptic seizures [11]. However, it remains
unknown whether the alternation of the ENK level is
one of the reasons for the development of epilepsy, or
if it is a consequence of this pathology.
100bp
1 12 23 34 4
100bp
250bp
723bp
pENK
251bp
GAPDH
Molecular
mass
Molecular
mass
500bp
500bp750bp
750bp1000bp
1000bp2000bp
2000bp
F i g. 2. Expression of proenkephalin (pENK) mRNA (vertical scale, OD pENK/OD GAGPH) in hippocampal neurons of the rats. 1-4)
Animal groups: blank control group, NS+NS+0.5NS, no seizure (1), negative control group, NS+ SVHRP+0.5NS, no seizure (2), model
group, KA+NS+0.5KA, seizure (3), and therapy group, KA+SVHRP+0.5KA (4).
Р и с. 2. Експресія мРНК проенкефаліну (пЕНК; вертикальна шкала, OD pENK/OD GAGPH) у нейронах гіпокампа щурів.
0.5
0
1 2 3 4
1.0
1.5
2.0
2.5
3.0
3.5
4.0
**
F i g. 3. The OD pENK/OD in hippocampal neurons of the rats.
**P < 0.01 vs the control groups and therapy group.
Р и с. 3. OD pENK/OD у нейронах гіпокампа щурів.
prognosis among all types of seizures; about 60-
70% of all patients of such a group have intractable
seizures. It should be recognized that the mechanisms
of TLE are still unclear. Kainic acid is a structural
analog of an excitatory amino acid neurotransmitter,
glutamate. Single systemic injections of a convulsive
NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 4 361
EFFECTS OF SCORPION VENOM HEAT-RESISTANT PROTEIN
Our study suggests that SVHRP strongly inhibits
the formation of the epilepsy sensitivity, and it
also reduces the expression of pENK mRNA in the
hippocampus of sensitive animals in the model of
epilepsy. Thus, SVHRP-related inhibition of the
sensitivity with respect to epilepsy correlates with
normalization of abnormal overexpression of ENK
in one of the brain structures whose role in the
development of epilepsy is crucial. These facts may
provide a clue for understanding the mechanism of
TLE.
The experiments were carried out in accordance with the
internationally accepted and institutional ethical norms related
to the studies on vertebrate animals.
The authors, Y. Sun, X. Cui, Sh. Yin, D. Yu, Sh. Li,
W. Zhang, and J. Zhao, have no conflict of interests.
This work was supported by grants from the National
Natural Science Foundation of China, No. 31171037/c090202,
the Liaoning Province Education Department Scientific
Technological Research, LS2010057, and the Doctoral Fund
of the Ministry of Education of China for Youth Scholars
(20092105120006).
Йі. Сан1, К. Куї2, Ш. Йін3, Д. Йу3, Ш. Ли4, У. Жан3,
Дж. Жао3
ВПЛИВ ТЕРМОСТІЙКОГО ПРОТЕЇНУ З ОТРУ-
ТИ СКОРПІОНА НА СУДОРОЖНУ ПОВЕДІНКУ ТА
ЕКСПРЕСІЮ ПРОЕНКЕФАЛІНУ У ЩУРІВ З ВИКЛИКА-
НОЮ КАЇНАТОМ ЕПІЛЕПСІЄЮ
1 Функціональна лабораторія, Далянський медичний
університет, Далянь (Китай).
2 Студент-медик, Далянський медичний університет,
Далянь (Китай).
3 Відділ фізіології, Далянський медичний університет,
Далянь (Китай).
4 Аспірант-медик, Далянський медичний університет,
Далянь (Китай).
Р е з ю м е
Отрута скорпіона є традиційним антиепілептичним тера-
певтичним засобом в Азії. Ми вивчали вплив термостійкого
протеїну з отрути скорпіона (ТСПОС) на судорожну пове-
дінку щурів з викликаною каїнатом епілепсією та на експре-
сію проенкефаліну (пEНК) у їх гіпокампі. Підшкірні ін’єкції
«конвульсивних» доз каїнової кислоти (КК, 10 мг/кг) при-
зводили до розвитку гострих епілептичних судом; інтенсив-
ність таких судом вимірювали після наступних ін’єкцій КК
(5 мг/кг, підпорогова доза в нормі). Частина тварин отри-
мувала ТСПОС у дозі 125 мкг/кг шляхом внутрішньоочере-
винних ін’єкцій щоденно протягом 10 днів; щурам контр-
ольної групи вводили фізіологічний розчин. Вимірювали
поведінкові показники; гіпокамп ізолювали для подальшої
оцінки пEНК мРНК з використанням RT-PCR-аналізу. Усе-
реднені поведінкові показники судомної чутливості в групі
тварин, котрі отримували ТСПОС, були істотно нижче (P <
< 0.05) таких у контрольній групі (1.19 проти 2.93). У не-
йронах гіпокампа щурів із високою судомною чутливістю,
котрі отримували КК, рівень пЕНК мРНК був істотно ви-
щим, тоді як у тварин з ін’єкціями ТСПОС відповідний по-
казник був значно нижчим. Отже, ТСПОС гальмує пове-
дінкові судоми при епілепсії та різко зменшує аномально
збільшений рівень пEНК мРНК у нейронах гіпокампа та-
ких тварин.
REFERENCES
1. S. M. Yin, Z. Guan, Y. Tang, et al., “Abnormal expression of
epilepsy-related gene ERG1/NSF in the spontaneous recurrent-
seizure rats with spatial learning memory deficits induced by
kainic acid,” Brain Res., 1053, 195-202 (2005).
2. M. Obeid, J. Frank, M. Medina, et al., “Neuroprotective effects
of leptin following kainic acid-induced status epilepticus,”
Epilepsy Behav., 19, No. 3, 278-283 (2010).
3. J. S. Han, Principles of Neuroscience [in Chinese], Peking
Univ. Press, Beijing (1999).
4. J. S. Hong, P. L. Wood, and J. C. Ggillin, “Changes of
hippocampal met-enkephalin content after recurrent motor
seizures,” Nature, 285, No. 5762, 231-232 (1980).
5. J. S. Hong, J. F. McGinty, P. H. Lee, et al., “Relationship
between hippocampal opioid peptides and seizures,” Prog.
Neurobiol., 40, No. 4, 507-528 (1993).
6. Y. H. Kim, S. S. Choi, J. K. Lee, et al., “Possible roles of JNK
pathway in the regulation of hippocampal proenkephalin and
immediate early gene expression induced by kainic acid,” Mol.
Cells, 11, No. 2, 144-150 (2001).
7. R. J. Lee, J. S. Hong, J. F. McGinty, et al., “Increased
enkephalin and dynorphin immunoreact ivi ty in the
hippocampus of seizure-sensitive Mongolian gerbils,” Brain
Res., 401, No. 2, 353-358 (1987).
8. M. E. Moneta and V. Höllt, “Perforant path kindling induces
differential alterations in the mRNA levels coding for
prodynorphin and proenkephalin in the rat hippocampus,”
Neurosci. Lett., 110, No. 3, 273-278 (1990).
9. L. Chen, “Enkephalin, neuropeptide Y, NSE and epilepsy,”
Fore Med. Inform., 25, No. 1, 7-10 (2004).
10. C. J. Schindler, R. Slamberová, A. Rimanуczy, et al., “Field-
specific changes in hippocampal opioid mRNA, peptides, and
receptors due to prenatal morphine exposure in adult male
rats,” Neuroscience, 126, No. 2, 355-364 (2004).
11. H. S. Noh, D. W. Kim, S. S. Kang, et al., “Ketogenic diet
decreases the level of proenkephalin mRNA induced by kainic
acid in the mouse hippocampus,” Neurosci. Lett., 395, No. 1
87-92 (2006).
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