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Effects of pre-pregnancy chronic valproate administration in female rats on avoidance memory and hippocampal gene expression of offspring

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Effects of Pre-pregnancy Chronic Valproate Administration in Female Rats on Avoidance Memory and Hippocampal Gene

Expression of Offspring

Masoumeh Gholami1,2, Tina Rahjoo3, Faranak Jafari1,

Jamal Amri4, Mehdi Sadegh5,6

1 AssistantProfessor, Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

2 AssistantProfessor, Department of Physiology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

3 MSc in Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

4 MSc in Biochemistery, Traditional and Complementary Medicine Research Center, Arak University of Medical Sciences, Arak, Iran

5 Molecular and Medicine Research Center, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran

6 AssociateProfessor, Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran (Received December 11, 2019 ; Accepted Janary 29, 2020)

Abstract

Background and purpose: Valproic acid derivatives are histone deacetylases (HDACs) inhibitors.

HDACs are important in epigenetic processes. Some epigenetic modifications are inherited. This study aimed at investigating the intergenerational effects of pre-pregnancy chronic valproate consumption on offspring.

Materials and methods: In this experimental study, twelve female Wistar rats were randomly divided into two groups of control and valproate. For 30 days, the control group received saline and the valproate group received sodium valproate (300 mg/kg) intraperitoneally (i.p.). After mating, pregnancy, and nursing, two males and two females pup were randomly selected from the mothers and placed in the following groups: 1) male offspring of the control group, 2) female offspring of the control group, 3) male offspring of the valproate group, and 4) female offspring of the valproate group. Future experiments were followed using these groups. Avoidance memory was assessed using the shuttle box. Offspring's hippocampus were extracted and used for MECP2, HDAC2, BDNF genes expression study by qRT-PCR.

Results: No significant differences were detected in avoidance memory between male and female offspring of the mothers in valproate group and that of the controls (P>0.05). There were no significant differences in MECP2, HDAC2, and BDNF genes expression between male offspring of the mothers in control and valproate groups (P>0.05). But, expression levels of these genes significantly decreased in female offspring of valproate mothers compared with those of the female offspring of the controls (P<0.05).

Conclusion: Pre-pregnancy chronic valproate consumption did not affect avoidance memory in offspring. But, it seems to affect hippocampus gene expression sex-dependently.

Keywords: avoidance memory, BDNF, HDAC2, MeCP2, valproate

J Mazandaran Univ Med Sci 2019; 29(182): 99-105 (Persian).

* Corresponding Author: Mehdi Sadegh- Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran (E-mail: [email protected])

Downloaded from jmums.mazums.ac.ir at 11:42 +0430 on Tuesday June 9th 2020

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هرود و ﺖﺴﯿﺑ ﻢﻬﻧ هرﺎﻤﺷ 182 ﺪﻨﻔﺳا لﺎﺳ 1398 ) 105 - 99 (

ﺮﺑ هدﺎﻣ يﺎﻫ تر رد يرادرﺎﺑ زا ﺶﯿﭘ تاوﺮﭙﻟاو ﻦﻣﺰﻣ ﺰﯾﻮﺠﺗ تاﺮﺛا ﯽﺳرﺮﺑ ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ ﺖﻓﺎﺑ رد ﺎﻫ نژ نﺎﯿﺑ و ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ

ﯽﻣﻼﻏ ﻪﻣﻮﺼﻌﻣ

1 و

2

ﻮﺠﻫر ﺎﻨﯿﺗ 3

يﺮﻔﻌﺟ ﮏﻧاﺮﻓ 1

يﺮﻣا لﺎﻤﺟ 4

قدﺎﺻ يﺪﻬﻣ

5 و

6

هﺪﯿﮑﭼ

ﺎﺳ ﻪﻘﺑ :فﺪﻫ و

،تاوﺮﭙﻟاو تﺎﻘﺘﺸﻣ رﺎﻬﻣ

ﺮﮔ زﻼﯿﺘﺳاد نﻮﺘﺴﯿﻫ .ﺪﻨﺘﺴﻫ ﺎﻫ

زﻼﯿﺘﺳاد نﻮﺘﺴﯿﻫ ﻢــﻬﻣ ﮏــﯿﺘﻧژ ﯽﭘا ﺪﻨﯾاﺮﻓ رد ﺎﻫ

ﯽﻣ ﯽﻣ ثرا ﻪﺑ ﮏﯿﺘﻧژ ﯽﭘا تاﺮﯿﯿﻐﺗ ﯽﺧﺮﺑ .ﺪﻨﺷﺎﺑ ﯽﻠــﺴﻧ ﻦﯿــﺑ تاﺮــﺛا ،ﻪﻌﻟﺎﻄﻣ ﻦﯾا رد .ﺪﻨﺳر

فﺮــﺼﻣ ﻦﻣﺰــﻣ وﺮــﭙﻟاو تا زا ﺶﯿــﭘ

يرادرﺎﺑ

، .ﺪﺷ ﯽﺳرﺮﺑ ناﺪﻧزﺮﻓ رد

شور و داﻮﻣ :ﺎﻫ

ا رد ،ﯽﺑﺮﺠﺗ ﻪﻌﻟﺎﻄﻣ ﻦﯾ 12

.ﺪــﻨﺘﻓﺮﮔ راﺮــﻗ تاوﺮــﭙﻟاو و لﺮــﺘﻨﮐ ناردﺎــﻣ هوﺮــﮔ ود رد ﯽﻓدﺎﺼﺗ هدﺎﻣ تر

تﺪﻣ 30 ) تاوﺮــﭙﻟاو ﻢﯾﺪــﺳ ،تاوﺮﭙﻟاو ناردﺎﻣ و ﻦﯿﻟﺎﺳ ،لﺮﺘﻨﮐ ناردﺎﻣ ﻪﻧازور ،زور mg/kg

300 ﺖــﻓﺎﯾرد ﯽﻗﺎﻔــﺻ ﻞــﺧاد ار (

ﺖﻔﺟ زا ﺲﭘ .ﺪﻧدﺮﮐ ردﺎﻣ ﺮﻫ هدﺎﻣ و ﺮﻧ ناﺪﻧزﺮﻓ زا ﯽﻫدﺮﯿﺷ و يرادرﺎﺑ ،يﺮﯿﮔ

، 2 ﺮــﯾز يﺎــﻫ هوﺮــﮔ و بﺎﺨﺘﻧا ﯽﻓدﺎﺼﺗ ناﻮﯿﺣ

):ﺪﺷ دﺎﺠﯾا 1

) ،لﺮﺘﻨﮐ ناردﺎﻣ ﺮﻧ ناﺪﻧزﺮﻓ ( 2

) ،لﺮﺘﻨﮐ ناردﺎﻣ هدﺎﻣ ناﺪﻧزﺮﻓ ( 3

) و تاوﺮــﭙﻟاو ناردﺎــﻣ ﺮــﻧ ناﺪــﻧزﺮﻓ ( 4

ناﺪــﻧزﺮﻓ (

هوﺮﮔ ﻦﯾا .تاوﺮﭙﻟاو ناردﺎﻣ هدﺎﻣ ﺶﯾﺎﻣزآ ياﺮﺑ ﺎﻫ

هزاﺪﻧا ﺲﮐﺎﺑ ﻞﺗﺎﺷ ﺎﺑ ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ .ﺪﻧﺪﺷ هدﺎﻔﺘﺳا يﺪﻌﺑ يﺎﻫ .ﺪــﺷ يﺮــﯿﮔ

نژ نﺎﯿﺑ و جاﺮﺨﺘﺳا ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ يﺎﻫ

MECP2, HDAC2, BDNF شور ﺎﺑ

qRT-PCR .ﺪﺷ ﯽﺳرﺮﺑ

ﻪﺘﻓﺎﯾ :ﺎﻫ ﻨﻌﻣ ﺮﯿﯿﻐﺗ ﯽ ناﺪﻧزﺮﻓ ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ رد يراد هﺪﻫﺎﺸﻣ لﺮﺘﻨﮐ هدﺎﻣ و ﺮﻧ ناﺪﻧزﺮﻓ ﻪﺑ ﺖﺒﺴﻧ تاوﺮﭙﻟاو ناردﺎﻣ هدﺎﻣ و ﺮﻧ

) ﺪﺸﻧ 05 /0 P>

نژ نﺎﯿﺑ .(

يﺎﻫ MECP2, HDAC2, BDNF ﻓ رد

ار يرادﺎﻨﻌﻣ توﺎﻔﺗ ﻢﻫ ﺎﺑ تاوﺮﭙﻟاو و لﺮﺘﻨﮐ ناردﺎﻣ ﺮﻧ ناﺪﻧزﺮ

) داﺪﻧ نﺎﺸﻧ 05

/0 P>

نژ ﻦﯾا نﺎﯿﺑ ﻪﮐ ﯽﻟﺎﺣ رد ،(

ﯽﻨﻌﻣ ﺶﻫﺎﮐ ،تاوﺮﭙﻟاو هدﺎﻣ ناﺪﻧزﺮﻓ رد ﺎﻫ هدﺎــﻣ ناﺪــﻧزﺮﻓ ﺎــﺑ ﻪﺴﯾﺎﻘﻣ رد يراد

ﺖﺷاد لﺮﺘﻨﮐ )

05 /0 P<

(.

:جﺎﺘﻨﺘﺳا ﺟا يﺮﯿﮔدﺎﯾ رد يﺮﯿﺛﺎﺗ يرادرﺎﺑ زا ﺶﯿﭘ تاوﺮﭙﻟاو ﻦﻣﺰﻣ فﺮﺼﻣ ﯽﻣ ﺮﻈﻧ ﻪﺑ ﺪﻨﭼ ﺮﻫ .ﺖﺷاﺪﻧ ناﺪﻧزﺮﻓ ﯽﺑﺎﻨﺘ

ﺪﺳر

ﯽﻣ نژ نﺎﯿﺑ ﺲﻨﺟ ﻪﺑ ﻪﺘﺴﺑاو ترﻮﺻ ﻪﺑ ﺪﻧاﻮﺗ يﺎﻫ

.دزﺎﺴﺑ ﺮﺛﺎﺘﻣ ﭗﻤﮐﻮﭙﯿﻫ رد ار ﯽﻤﯿﻈﻨﺗ

:يﺪﯿﻠﮐ يﺎﻫ هژاو

،ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ ،BDNF

HDAC2 ، MeCP2 تاوﺮﭙﻟاو ،

ﻪﻣﺪﻘﻣ

ﺪﯿﺳا ﮏﯿﯾوﺮﭙﻟاو نآ تﺎﻘﺘــﺸﻣ و

عﺮــﺻ لﺮــﺘﻨﮐ رد و

ﻪــﺑ ﺞﻨــﺸﺗ ﯽﻣ رﺎــﮐ ﯿــﻨﭽﻤﻫ ،ﺪــﻧور ﻦ

ﺮﯾﺎــﺳ لﺮــﺘﻨﮐ ياﺮــﺑ

يرﺎﻤﯿﺑ دردﺮــﺳ ﺮــﯿﻈﻧ ﯽﺒــﺼﻋ ﻢﺘــﺴﯿﺳ يﺎﻫ يﺎﻫ

،ﯽــﻧﺮﮕﯿﻣ ﯽــﺒﻄﻗ ود لﻼﺘــﺧا و ﯽﮔدﺮﺴﻓا ،ﺎﯿﻧﺎﻣ

ﺪــﻧراد دﺮﺑرﺎــﮐ )1

، 2(

.

ﺪﯿﺳا ﮏﯿﯾوﺮﭙﻟاو ﮏﯾ

بﺮﭼ ﺪﯿﺳا 8

ﻪﻨﺑﺮﮐ ﺖﺳا ﻪﮐ ﺪــﺳ زا

ﯽﻣ رﻮﺒﻋ يﺰﻐﻣ ﯽﻧﻮﺧ ﺪﻨﮐ

)2 ﺪﯿﺳا ﮏﯿﯾوﺮﭙﻟاو (.

ناﻮﻨﻋ ﻪﺑ

:لﻮﺌﺴﻣ ﻒﻟﻮﻣ قدﺎﺻ يﺪﻬﻣ

كارا- : كارا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﯽﮑﺷﺰﭘ هﺪﮑﺸﻧاد ،

[email protected] Email:p

1 . ،رﺎﯾدﺎﺘﺳا ا ،ﻪﯾرﺪﯿﺣ ﺖﺑﺮﺗ ،ﻪﯾرﺪﯿﺣ ﺖﺑﺮﺗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،بﺎﺼﻋا مﻮﻠﻋ تﺎﻘﯿﻘﺤﺗ ﺰﮐﺮﻣ ناﺮﯾ

2 . ،رﺎﯾدﺎﺘﺳا ناﺮﯾا ،ﻪﯾرﺪﯿﺣ ﺖﺑﺮﺗ ،ﻪﯾرﺪﯿﺣ ﺖﺑﺮﺗ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﯽﮑﺷﺰﭘاﺮﯿﭘ هﺪﮑﺸﻧاد ،يژﻮﻟﻮﯾﺰﯿﻓ هوﺮﮔ

3 . ﺪﺷرا ﯽﺳﺎﻨﺷرﺎﮐ ناﺮﯾا ،كارا ،كارا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﯽﮑﺷﺰﭘ هﺪﮑﺸﻧاد ،يژﻮﻟﻮﯾﺰﯿﻓ

4 . ﻨﺷرﺎﮐ ،ﯽﻤﯿﺷﻮﯿﺑ ﺪﺷرا س ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﻞﻤﮑﻣ و ﯽﺘﻨﺳ ﺐﻃ تﺎﻘﯿﻘﺤﺗ ﺰﮐﺮﻣ

ناﺮﯾا ،كارا ،كارا

5.

،ﯽﻟﻮﮑﻠﻣ ﯽﮑﺷﺰﭘ تﺎﻘﯿﻘﺤﺗ ﺰﮐﺮﻣ ،ﯽﮑﺷﺰﭘ هﺪﮑﺸﻧاد

ناﺮﯾا ،كارا ،كارا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد

6 . هوﺮﮔ ،رﺎﯿﺸﻧاد ناﺮﯾا ،كارا ،كارا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ،ﯽﮑﺷﺰﭘ هﺪﮑﺸﻧاد ،يژﻮﻟﻮﯾﺰﯿﻓ

: ﺖﻓﺎﯾرد ﺦﯾرﺎﺗ 20

/9 / 1398 : تﺎﺣﻼﺻا ﺖﻬﺟ عﺎﺟرا ﺦﯾرﺎﺗ 25

/9 / 1398 : ﺐﯾﻮﺼﺗ ﺦﯾرﺎﺗ 29

/ 10 / 1398

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ﯽﻣﻼﻏ ﻪﻣﻮﺼﻌﻣ نارﺎﮑﻤﻫ و

نارﺪﻧزﺎﻣ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﻪﻠﺠﻣ

ﺷ ،ﻢﻬﻧ و ﺖﺴﯿﺑ هرود

هرﺎﻤ 182 ﺪﻨﻔﺳا ، 1398 101

هﺎﺗﻮﮐ شراﺰﮔ

هﺪﻨﻨﮐرﺎﻬﻣ زﻼﯿﺘﺳاد نﻮﺘﺴﯿﻫ نﻮﺘــﺴﯿﻫ نﻮﯿــﺳﻼﯿﺘﺳا ﺮﯿﯿﻐﺗ ﺎﺑ

ﺎــﻫ

نژ نﺎــﯿﺑ ﺮــﯿﯿﻐﺗ و موزﻮــﻣوﺮﮐ رﺎﺘﺧﺎــﺳ ﺮــﯿﯿﻐﺗ ﺐﺒــﺳ ﺎــﻫ

ﯽﻣ دﻮــﺷ )3

، 4(

ﻪــﻠﻣﺎﺣ نﺎــﻧز. يرادرﺎــﺑ نارود رد ﻪــﮐ يا

ﺪﯿﺳا ﮏﯿﯾوﺮﭙﻟاو ﯽﻣ هدﺎﻔﺘﺳا

ﻨﮐ نﺎﮐدﻮﮐ يدﺎﯾز لﺎﻤﺘﺣا ﺎﺑ ،ﺪﻨ

ﯽﻣ ﺎﯿﻧد ﻪﺑ ﻢﺴﯿﺗوا ﻪﺒﺷ ﯽﺒﺼﻋ تﻻﻼﺘﺧا ياراد ﺪﻧدروآ

)7 - . 5(

دﻮــﺟو ﯽــﻌﻨﻣ يرادرﺎﺑ زا ﺶﯿﭘ نآ فﺮﺼﻣ ياﺮﺑ دﻮﺟو ﻦﯾا ﺎﺑ .دراﺪﻧ نﻮﺘﺴﯿﻫ ﺎﻫزﻼﯿﺘــﺳاد )

آ وﺰــﺟ (HDAC ﻢﯾﺰــﻧ ﯾﺎــﻫ ﯽ

ﻪﮐ ﺪﻨﺘﺴﻫ ﺮﺠﻨﻣ ﻮﺘﺴﯿﻫ نﻮﯿﺳﻼﯿﺘﺳاد ﻪﺑ ن

ﺎﻫ ﺖﯿﻌﺿو ﺮﯿﯿﻐﺗ و

ﻦﯿﺗﺎﻣوﺮﮐ ﯽــﻣ

ﺪﻧﻮــﺷ )8 ﻪﺨــﺴﻧ ﺮﮔرﺎــﻬﻣ رﻮﺘﮐﺎــﻓ (.

يرادﺮــﺑ

) MeCP2 (

methyl-CpG binding protein 2 نﺪﻧاﻮﺧاﺮﻓ ﺎﺑ

ﻪــﻠﯿﺘﻣ ﯽﺣاﻮــﻧ ﻪــﺑHDAC نﺪــﺷ ﻪﻠﯿﺘــﺳاد ﺐﺒــﺳDNA

نﻮﺘــﺴﯿﻫ رد و ﯽﺣاﻮــﻧ ﻦــﯾا رد ﺎــﻫ نﺪــﺷ لﺎــﻌﻓﺮﯿﻏ ﻪــﺠﯿﺘﻧ

ﯽﻣ ﻦﯿﺗﺎﻣوﺮﮐ دﻮﺷ

)9 ﺪﯿﺳا ﮏﯿﯾوﺮﭙﻟاو(.

زﻼﯿﺘﺳاد نﻮﺘﺴﯿﻫ ﺎﻫ

ﯽﻣ رﺎﻬﻣ ار ﺪــﻨﮐ

ﻪــﻬﺟاﻮﻣ ﻦﯾاﺮﺑﺎــﻨﺑ . ﺪﯿــﺳا ﮏــﯿﯾوﺮﭙﻟاو ﺎــﺑ

ﯽﻣ ﺪــﻧاﻮﺗ ژ ن شﻮﻣﺎــﺧ يﺎــﻫ زﺎﺑ ار

نﻮﺘــﺴﯿﻫ .ﺪــﻨﮐ لﺎــﻌﻓ

) ود عﻮــﻧ زﻼﯿﺘﺳاد HDAC2

ﻢــﻬﻣ يﺎــﻫرﻮﺘﮐﺎﻓ ﻪــﻠﻤﺟ زا (

ﯽــﻣ ﮏﯿﺘﻧژ ﯽﭘا تاﺮﯿﯿﻐﺗ رد ﺪﻨــﺷﺎﺑ

) 10 ﺮﮕﻧﺎــﯿﺑ تﺎــﻌﻟﺎﻄﻣ (.

ﻢﻬﻣ ﺶﻘﻧ HDAC2 و MeCP2 ﯽﭘا يﺎﻫﺪﻨﯾاﺮﻓ رد ﮏﯿﺘﻧژ

نآ ﺖﯿﻟﺎﻌﻓ ﺮﯿﯿﻐﺗ هﺪﺷ ﺺﺨﺸﻣ و ﺖﺳا نﺎــﯿﺑ ﺮﯿﯿﻐﺗ ﺐﺒﺳ ﺎﻫ

نژ ﺮﯾﺎﺳ ﮏﯿﻓوﺮﺗورﻮﻧ رﻮﺘﮐﺎﻓ ﻪﻠﻤﺟ زا لﻮﻠﺳ ﯽﻤﯿﻈﻨﺗ يﺎﻫ

) يﺰﻐﻣ ﻪﺑ (BDNF ﯽﻣ ﭗﻤﮐﻮﭙﯿﻫ رد هﮋﯾو دﻮــﺷ

) 11 (.

BDNF

نژ نﺎﯿﺑ ﻢﯿﻈﻨﺗ رد ﯽﻧورﻮــﻧ ﺰﯾﺎﻤﺗ و ﺪﺷر يﺎﻫﺪﻨﯾاﺮﻓ ﯽﻃ ﺎﻫ

ﻞﮑﺷ يﺎﻫﺪﻨﯾاﺮﻓ ﯽﻃ ﻦﯿﻨﭽﻤﻫ و ﭗــﻤﮐﻮﭙﯿﻫ ﯽﺴﭘﺎﻨﯿﺳ يﺮﯾﺬﭘ

ﯽﻣ ﻪــﻈﻓﺎﺣ و يﺮﯿﮔدﺎــﯾ ﻪــﺑ ﺮــﺠﻨﻣ ﻪﮐ ﻞــﺑﺎﻗ ﺶــﻘﻧ ،ﺪﻧﻮــﺷ

دراد ﯽﻬﺟﻮﺗ )

12

، 13 (.

ﯽﭘا تاﺮﺛا ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ ﻦﯿــﻨﭽﻤﻫ و تاوﺮــﭙﻟاو ﮏــﯿﺘﻧژ

ﯽﭘا تاﺮﺛا ﻦﯾا ﯽﻠﺴﻧ ﻦﯿﺑ لﺎﻘﺘﻧا لﺎﻤﺘﺣا لاﻮﺳ ﻦﯾا ،ﮏﯿﺘﻧژ

ﯽﻣ حﺮﻄﻣ زا ﺶﯿــﭘ تاوﺮــﭙﻟاو ﻦﻣﺰــﻣ فﺮﺼﻣ ﺎﯾآ ﻪﮐ دﻮﺷ

ﯽﻠﻋو هدﺎﻣ ﺲﻨﺟرد يرادرﺎﺑ مﺪﻋ ﻢﻏر

،يرادرﺎﺑ ﻦﯿﺣ فﺮﺼﻣ

ﯽﻣ ﺦــﺳﺎﭘ ياﺮﺑ .ﺪﻨﮐ دﺎﺠﯾا ناﺪﻧزﺮﻓ رد ار ﯽﺿراﻮﻋ ﺪﻧاﻮﺗ هرود ﮏــﯾ يﺎﻫﺪــﻣﺎﯿﭘ ،ﺮــﺿﺎﺣ ﻪــﻌﻟﺎﻄﻣ رد ﺶــﺳﺮﭘ ﻦﯾا ﻪﺑ

تر رد ﻢﯾﺪﺳ تاوﺮﭙﻟاو فﺮﺼﻣ ﻦﻣﺰﻣ زا ﺶﯿــﭘ هدﺎﻣ يﺎﻫ

نژ نﺎﯿﺑ ﺮﺑ ار يرادرﺎﺑ ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ رد ﯽﻤﯿﻈﻨﺗ يﺎﻫ

.ﻢﯾدﺮﮐ ﯽﺳرﺮﺑ ناﺪﻧزﺮﻓ ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ ﻦﯿﻨﭽﻤﻫ و

ﺎﻫ شور و داﻮﻣ

ا رد

،ﯽﺑﺮﺠﺗ ﻪﻌﻟﺎﻄﻣ ﻦﯾ 12

ﺮــﻧ تر ﮏــﯾ و هدﺎﻣ تر

) ناﻮﺟ ﻎﻟﺎﺑ رﺎﺘﺴﯾو داﮋﻧ 9

- 10 دراو ﺪــﻟاو ناﻮــﻨﻋ ﻪــﺑ (ﻪﺘﻔﻫ

ﻂﯾاﺮــﺷ و ﺎــﻣد رد تﺎــﻧاﻮﯿﺣ .ﺪﻧﺪــﺷ ﻪــﻌﻟﺎﻄﻣ 12

ﺖﻋﺎــﺳ

و ﯽﯾﺎﻨﺷور 12

و بآ ﻪــﺑ دازآ ﯽﺳﺮﺘﺳد ﺎﺑ ﯽﮑﯾرﺎﺗ ﺖﻋﺎﺳ

و وراد ﺎــﺑ يرادرﺎــﺑ زا ﺶﯿﭘ ﻪﻬﺟاﻮﻣ .ﺪﻧﺪﺷ يراﺪﻬﮕﻧ اﺬﻏ هدﺎــﻣآ اﺪــﻧزﺮﻓ ﻞــﺴﻧ يزﺎــﺳ تﺎــﻌﻟﺎﻄﻣ سﺎــﺳا ياﺮــﺑ ن

ﯽﻠﺒﻗ ) 14

، 15 تر ،ﻪــﻌﻟﺎﻄﻣ عوﺮﺷ رد .ﺖﻓﺮﮔ ترﻮﺻ( يﺎــﻫ

:ﺪﻨﺘﻓﺮﮔ راﺮﻗ هوﺮﮔ ود رد ﯽﻓدﺎﺼﺗ ترﻮﺻ ﻪﺑ هدﺎﻣ

1 - ) تاوﺮــﭙﻟاو ناردﺎــﻣ هوﺮﮔ 6

= تر :(n ﻪــﻧازور ﺎــﻫ

5/

0 ﯽــﻠﯿﻣ زود ﺎــﺑ ﻢﯾﺪــﺳ تاوﺮــﭙﻟاو ﺮــﺘﯿﻟ mg/kg

300 ﻪــﺑ

تﺪﻣ 30 زور ﯽﻣ ﺖﻓﺎﯾرد ﯽﻗﺎﻔﺻ ﻞﺧاد و ﺪﻧدﺮﮐ

) 16 (.

2 - ) لﺮﺘﻨﮐ ناردﺎﻣ 6

= ﻪــﻧازور :(n 5/

0 ﯽــﻠﯿﻣ لﺎــﻣﺮﻧ ﺮــﺘﯿﻟ

تﺪﻣ ﻪﺑ ﻦﯿﻟﺎﺳ 30

ﯽﻣ ﺖﻓﺎﯾرد ﯽﻗﺎﻔﺻ ﻞﺧاد زور .ﺪﻧدﺮﮐ

نﺪــﺷ كﺎــﭘ ياﺮــﺑ) تﺎــﻘﯾرﺰﺗ نﺎﯾﺎﭘ زا ﺲﭘ ﻪﺘﻔﻫ ود

،(تاوﺮﭙﻟاو ﺎﺑ ﻦﯿﻨﺟ ﻢﯿﻘﺘﺴﻣ ﻦﺘﺷاﺪﻧ سﺎﻤﺗ و نﺪﺑزا تاوﺮﭙﻟاو ﺖﻔﺟ تر ﺎﺑ ﺮﻧ تر حﺎﻘﻟ و يﺮﯿﮔ ياﺮﺑ .ﺪﺷ مﺎﺠﻧا هدﺎﻣ يﺎﻫ

ا يﺮﯿﮔﻮﻠﺟ رد يرﺪــﭘ مﻮــﻧژ توﺎﻔﺗ ﯽﻟﺎﻤﺘﺣا ﺮﺛا ز

،ﺞﯾﺎــﺘﻧ

هدﺎﻣ ﺖــﻔﺟ ﺮــﻧ تر ﮏــﯾ ﺎــﺑ هوﺮــﮔ ود يﺎﻫ .ﺪﻧﺪــﺷ يﺮﯿﮔ

نﺎﯾﺎﭘ زا ﺪﻌﺑ .ﺪﺷ ﺪﯿﺋﺎﺗ يرادرﺎﺑ كﻼﭘ هﺪﻫﺎﺸﻣ ﺎﺑ يرادرﺎﺑ ﻪــﺑ ردﺎــﻣ ﺮــﻫ زا هدﺎــﻣ ﺪــﻧزﺮﻓ ود و ﺮــﻧ ﺪﻧزﺮﻓ ود ،ﯽﻫدﺮﯿﺷ ﯽــﺸﯾﺎﻣزآ هوﺮــﮔ رﺎــﻬﭼ رد و بﺎــﺨﺘﻧا ﯽﻓدﺎــﺼﺗ ترﻮــﺻ ) 12

= ترﻮﺻ ﻪﺑ (n ﺮﮔ راﺮﻗ ﺮﯾز

:ﺪﻨﺘﻓ

1 - ) لﺮــﺘﻨﮐ ناردﺎــﻣ هدﺎــﻣ ناﺪــﻧزﺮﻓ female cnt

،(

2 - ) لﺮــﺘﻨﮐ ناردﺎــﻣ ﺮﻧ ناﺪﻧزﺮﻓ male cnt

،(

3 - ناﺪــﻧزﺮﻓ

) تاوﺮــﭙﻟاو ناردﺎــﻣ هدﺎﻣ female valp

،(

4 - ﺮــﻧ ناﺪــﻧزﺮﻓ

) تاوﺮﭙﻟاو ناردﺎﻣ male valp

.(

ناﺪﻧزﺮﻓ زا ﯽﻤﯿﻧ ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ نﻮﻣزآ رد هوﺮﮔ ﺮﻫ

ﺑ ياﺮــﺑ ﺮﮕﯾد ﻢﯿﻧ و ﺲﮐﺎﺑ ﻞﺗﺎﺷ ﺎﺑ درﻮــﻣ نژ نﺎــﯿﺑ ﯽــﺳرﺮ

راﺮــﻗ هدﺎﻔﺘــﺳا .ﺪــﻨﺘﻓﺮﮔ

ﺶﯾﺎــﻣزآ هوﺮــﮔ رﺎــﻬﭼ يور ﺎــﻫ

ﯽﻨﺳ هدوﺪﺤﻣ رد ناﺪﻧزﺮﻓ 6

.ﺪﺷ مﺎﺠﻧا ﻪﺘﻔﻫ

ﺪــﺷ مﺎــﺠﻧا ﯽﻟاﻮــﺘﻣ زور ﻪﺳ رد ﺲﮐﺎﺑ ﻞﺗﺎﺷ نﻮﻣزآ )

17 (.

لوا زور ناﻮــﯿﺣ مود زور .دﻮــﺑ هﺎﮕﺘــﺳد ﺎــﺑ ناﻮﯿﺣ و ﯽﯾﺎﻨﺷآ

ﺗا نورد اﺪﺘﺑا قﺎــﺗا ود هﺪــﻨﻨﮐاﺪﺟ رد و ﺖﻓﺮﮔ راﺮﻗ ﻦﺷور قﺎ

Downloaded from jmums.mazums.ac.ir at 11:42 +0430 on Tuesday June 9th 2020

(4)

ناﻮــﯿﺣ ﺮــﻫ ياﺮــﺑ ﮏﯾرﺎﺗ قﺎﺗا ﻪﺑ دورو نﺎﻣز تﺪﻣ و ﺪﺷ زﺎﺑ .ﺪﺷ ﺖﺒﺛ كﻮﺷ ﺲﭙﺳ ) ﯽﮑﯾﺮﺘﮑﻟا

2 ﯽﻠﯿﻣ تﺪــﻣ ﻪــﺑ ﺮــﭙﻣآ 2

ﻪﺑﺎــﺸﻣ ﺶﯾﺎــﻣزآ ،مﻮﺳ زور رد .ﺪﺷ لﺎﻤﻋا ناﻮﯿﺣ ﻪﺑ (ﻪﯿﻧﺎﺛ .ﺪﺷ راﺮﮑﺗ ﯽﮑﯾﺮﺘﮑﻟا كﻮﺷ نوﺪﺑ ﯽﻟو لوا زور ﻞﮑﺗوﺮﭘ

،نژ نﺎــﯿﺑ ﯽــﺳرﺮﺑ ياﺮــﺑ جاﺮﺨﺘــﺳا

ﺖــﻓﺎﺑ زاRNA

ﺖــﯿﻤﮐ .ﺪــﺷ مﺎــﺠﻧا لوﺰــﯾاﺮﺗ لﻮــﻠﺤﻣ ﻂــﺳﻮﺗ ﭗﻤﮐﻮﭙﯿﻫ ﺰﺘﻨــﺳ .ﺪــﺷ ﻦﯿــﯿﻌﺗ پاردﻮﻧﺎﻧ ﻂﺳﻮﺗ هﺪﺷ جاﺮﺨﺘﺳاRNA

ﺖﮐﺮــﺷ ﺖﯿﮐ ﻂﺳﻮﺗcDNA Pars tous

(ناﺮــﯾا ،نﺎــﺳاﺮﺧ)

زا مﺮــﮔوﺮﮑﯿﻣ ﮏــﯾ .ﺪــﺷ مﺎﺠﻧا دراو هﺪــﺷ ﺰﺘﻨــﺳcDNA

ﺶﻨــﮐاو Real time PCR يﺎــﻫﺮﻤﯾاﺮﭘ ﯽﻟاﻮــﺗ .ﺪــﯾدﺮﮔ

ﺟ رد هدﺎﻔﺘﺳا درﻮﻣ هرﺎﻤﺷ لوﺪ

1 .ﺖﺳا هﺪﺷ ﻪﺋارا

هرﺎﻤﺷ لوﺪﺟ 1

ﺶﻨﮐاو رد هدﺎﻔﺘﺳا درﻮﻣ يﺎﻫﺮﻤﯾاﺮﭘ ﯽﻟاﻮﺗ: qRT-PCR

نژ ﺮﻤﯾاﺮﭘ ﯽﻟاﻮﺗ

ﯽﺳﺮﺘﺳد هرﺎﻤﺷ

GAPDH F:TCCCATTCTTCCACCTTTGATGCT

R:ACCCTGTTGCTGTAGCCATATTCAT NM-017008.4

BDNF F: CCATAAGGACGCGGACTTGT

R: GAGGCTCCAAAGGCACTTGA NM_012513.4

HDAC2 F: TGAAGGAGAAGGAGGTCGAA

R: GGATTTATCTTCTTCCTTAACGTCTG NM_053447.1

Mecp2 F:ATGGTAGCTGGGATGTTAGGG

R:TGAGCTTTCTGATGTTTCTGCTT NM_022673.2

اﺮﭘ ﺮﻤﯾ GAPDH هدﺎﻔﺘــﺳا ﯽــﻠﺧاد لﺮــﺘﻨﮐ ناﻮــﻨﻋ ﻪﺑ

مﺎــﺠﻧا ياﺮــﺑ .ﺪــﺷ qRT-PCR

ﻦﯾﺮـــﮔ ﺮﺒﯾﺎــﺳ شور زا

هﺎﮕﺘــﺳد) Roche داﻮــﻣ طﻮــﻠﺨﻣ .ﺪــﺷ هدﺎﻔﺘــﺳا (ﺲﯿﺋﻮــﺳ

ياﺮﺑ 40 ﯽﮕﺘﺷﺮﺳاو ﻞﻣﺎﺷ ﻪﺧﺮﭼ 10

يﺎــﻣد رد ﻪــﯿﻧﺎﺛ 95

ﯽﺘﻧﺎﺳ ﻪﺟرد لﺎﺼﺗا و داﺮﮔ

10 يﺎﻣد ياﺮﺑ ﻪﯿﻧﺎﺛ 58

ﻪــﺟرد

ﯽﺘﻧﺎﺳ ﮔ ﻂﺴﺑ و داﺮ 10

يﺎﻣد رد ﻪﯿﻧﺎﺛ 72

ﯽﺘﻧﺎﺳ ﻪﺟرد داﺮﮔ

راﺪﻘﻣ .ﺪﺷ هداد تراﺮﺣ ﻞﺿﺎﻔﺗ زاΔCT

و فﺪــﻫ نژCt

نژ GAPDH ﺲﭙﺳ .ﺪﺷ ﻪﺒﺳﺎﺤﻣ

هوﺮــﮔ ﻪﺑ ﺖﺒﺴﻧΔΔCT

تاﺮــﯿﯿﻐﺗ ناﺰــﯿﻣ ندروآ ﺖﺳد ﻪﺑ ياﺮﺑ.ﺪﺷ ﻪﺒﺳﺎﺤﻣ لﺮﺘﻨﮐ ) نژ نﺎﯿﺑ Fold change شور زا (

ΔΔct

2-

.ﺪــﺷ هدﺎﻔﺘــﺳا زا

يرﺎــﻣآ راﺰــﻓا مﺮــﻧ GraphPad Prism

ﻪﺨــﺴﻧ) 5 ياﺮــﺑ (

هداد لﺎــﻣﺮﻧ ﻊــﯾزﻮﺗ اﺪﺘﺑا .ﺪﺷ هدﺎﻔﺘﺳا يرﺎﻣآ ﻞﯿﻠﺤﺗ رد ﺎــﻫ

نﻮــﻣزآ ﺎــﺑ هوﺮــﮔ ﺮــﻫ Kolmogorov-Smirnov

درﻮــﻣ

راﺮﻗ ﯽﺳرﺮﺑ يرﺎــﻣآ يﺎــﻫﺮﺘﻣارﺎﭘ ﻪــﺴﯾﺎﻘﻣ ﺲﭙــﺳ و ﺖﻓﺮﮔ

نﻮــﻣزآ زا هدﺎﻔﺘــﺳا ﺎــﺑ ﯽــﺸﯾﺎﻣزآ هوﺮــﮔ رﺎــﻬﭼ ﻦﯿــﺑ يﺎــﻫ

ANOVA هداد .ﺪــﺷ مﺎــﺠﻧا ﻪــﻓﺮﻃود ﺎــﯾ ﻪــﻓﺮﻄﮑﯾ

ﻪــﺑ ﺎــﻫ ترﻮﺻ

Mean±SEM هﺪﺷ ﻪﺋارا

.ﺪــﻧا 05 /0

<

ﺺﺧﺎــﺷP

ﻨﻌﻣ ﯽ .ﺪﺷ ﻪﺘﻓﺮﮔ ﺮﻈﻧرد يراد

ﺚﺤﺑ و ﺎﻫ ﻪﺘﻓﺎﯾ

رد ﮏﯾرﺎﺗ قﺎﺗا ﻪﺑ ﻦﺷور قﺎﺗا زا دورو ﯽﻧﺎﻣز ﺮﯿﺧﺎﺗ ) لوا زور pre-training ) مود و (

post-training نﻮــﻣزآ (

هوﺮﮔ ﻦﯿﺑ ﺲﮐﺎﺑ ﻞﺗﺎﺷ يرﺎــﻣآ نﻮــﻣزآ ﺎــﺑ ﺶﯾﺎــﻣزآ يﺎــﻫ

two-way ANOVA نﻮﻣزآ ﺲﭘ و

Bonferroni ﻪﺴﯾﺎﻘﻣ

) ﺖﺳا هﺪﺷ رادﻮﻤﻧ

هرﺎﻤﺷ 1 لﺮــﺘﻨﮐ يﺎﻫﺮﻧ ،هوﺮﮔ ود ﺮﻫ رد .(

) تاوﺮﭙﻟاو و رادﻮﻤﻧ

هرﺎﻤﺷ -A 1 قﺎــﺗا زا دورو نﺎــﻣز ﺮﯿﺧﺎﺗ (

) نﻮــﻣزآ مود زور رد ﮏﯾرﺎﺗ قﺎﺗا ﻪﺑ ﻦﺷور Post-training

(

ﻨﻌﻣ ترﻮﺻ ﻪﺑ ﯽ

ﺶﯿــﺑ يراد لوا زور ﯽﻧﺎــﻣز ﺮﯿﺧﺎــﺗ زا ﺮــﺗ

) Pre-training ﺖﺳا (

) 05 /0

<

(P ﯽﻟﺎﺣرد ، ﻪــﮐ هوﺮــﮔ ود رد

هدﺎﻣ ) تاوﺮﭙﻟاو و لﺮﺘﻨﮐ يﺎﻫ رادﻮــﻤﻧ

هرﺎﻤــﺷ -B 1 ﺮﯿﺧﺎــﺗ ،(

توﺎــﻔﺗ لوا زور ﺮﯿﺧﺎــﺗ ﺎــﺑ ﻪــﺴﯾﺎﻘﻣ رد مود زور ﯽﻧﺎــﻣز ــﻨﻌﻣ ﯽ توﺎــﻔﺗ مود زور رد دﻮــﺟو ﻦــﯾا ﺎــﺑ .دراﺪــﻧ يراد

ﻨﻌﻣ ﯽ ﻦﯿــﻨﭽﻤﻫ و تاوﺮــﭙﻟاو يﺎﻫﺮﻧ و لﺮﺘﻨﮐ يﺎﻫﺮﻧ ﻦﯿﺑ يراد

هدﺎﻣ ﻦﯿﺑ هدﺎﻣ و لﺮﺘﻨﮐ يﺎﻫ راﺪﻧ دﻮﺟو تاوﺮﭙﻟاو يﺎﻫ

هرﺎﻤﺷ رادﻮﻤﻧ 1

فﺮﺼﻣ ﺮﺛا :

ﺮﺑ يرادرﺎﺑ زا ﻞﺒﻗ تاوﺮﭙﻟاو ﯽﺑﺎﻨﺘﺟا ﻪﻈﻓﺎﺣ

ﯽﻨﻌﻣ توﺎﻔﺗ .ناﺪﻧزﺮﻓ و تاوﺮﭙﻟاو يﺎﻫﺮﻧ ﺎﺑ لﺮﺘﻨﮐ يﺎﻫﺮﻧ ﻦﯿﺑ يراد

هدﺎﻣ ﻦﯿﺑ ﻦﯿﻨﭽﻤﻫ هدﺎﻣ ﺎﺑ لﺮﺘﻨﮐ يﺎﻫ

هداد .دراﺪﻧ دﻮﺟو تاوﺮﭙﻟاو يﺎﻫ ﺎﻫ

ترﻮﺻ ﻪﺑ

mean±SEM

ﺮﮕﻧﺎﯿﺑ * .ﺪﻧا هﺪﺷ ﻪﺋارا 05

/0

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ﻣ ردP

ﻪﺴﯾﺎﻘ

ﺎﻫ هوﺮﮔ ﻪﻤﻫ ياﺮﺑ .ﺖﺳا لوا زور ﺎﺑ 6

= ﯽﻣn

.ﺪﺷﺎﺑ

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(5)

ﯽﻣﻼﻏ ﻪﻣﻮﺼﻌﻣ نارﺎﮑﻤﻫ و

نارﺪﻧزﺎﻣ ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد ﻪﻠﺠﻣ

ﺷ ،ﻢﻬﻧ و ﺖﺴﯿﺑ هرود

هرﺎﻤ 182 ﺪﻨﻔﺳا ، 1398 103

هﺎﺗﻮﮐ شراﺰﮔ

نژ نﺎﯿﺑ ﯽﻤﮐ ﯽﺳرﺮﺑ ﺞﯾﺎﺘﻧ ﯽــﻤﯿﻈﻨﺗ يﺎﻫ

MECP2,

HDAC2, BDNF هوﺮــﮔ ﻦﯿــﺑ ﭗــﻤﮐﻮﭙﯿﻫ ﺖﻓﺎﺑ رد

يﺎــﻫ

نﻮــﻣزآ ﺎﺑ ﯽﺸﯾﺎﻣزآ one-way ANOVA

نﻮــﻣزآ ﺲــﭘ و

Bonferroni ) ﺖﺳا هﺪﺷ ﻪﺴﯾﺎﻘﻣ

رادﻮﻤﻧ هرﺎﻤﺷ 2 .(

اﺪــﻧزﺮﻓ ﻦﯿــﺑ ﻪــﻌﻟﺎﻄﻣ درﻮــﻣ نژ ﻪــﺳ ﺮــﻫ نﺎــﯿﺑ ﺮــﻧ ن

ﻨﻌﻣ توﺎﻔﺗ ،لﺮﺘﻨﮐ ﺮﻧ ناﺪﻧزﺮﻓ و تاوﺮﭙﻟاو ﯽ

نﺎﺸﻧ ار يراد

هدﺎــﻣ ناﺪــﻧزﺮﻓ و لﺮــﺘﻨﮐ هدﺎــﻣ ناﺪــﻧزﺮﻓ ﻦﯿــﺑ ﺎــﻣا .داﺪــﻧ ﻨﻌﻣ توﺎﻔﺗ تاوﺮﭙﻟاو ﯽ

ﻪــﮐ يرﻮــﻃ ﻪــﺑ ،ﺪــﺷ ﺪﻫﺎﺸﻣ يراد

رد تاوﺮــﭙﻟاو هدﺎــﻣ ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ رد نژ ﻪﺳ ﺮﻫ نﺎﯿﺑ ﻨﻌﻣ ﺶﻫﺎﮐ لﺮﺘﻨﮐ هدﺎﻣ ناﺪﻧزﺮﻓ ﺎﺑ ﻪﺴﯾﺎﻘﻣ ﯽ

نﺎــﺸﻧ ار يراد

اد د ) 01 /0

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(P ﯽﻣ ﺮﻈﻧ ﻪﺑ ﻦﯾاﺮﺑﺎﻨﺑ. زا ﺶﯿﭘ تاوﺮﭙﻟاو ﺪﺳر

نژ نﺎﯿﺑ ﺲﻨﺟ ﻪﺑ ﻪﺘﺴﺑاو ترﻮﺻ ﻪﺑ يرادرﺎﺑ ﯽــﻤﯿﻈﻨﺗ يﺎﻫ

.ﺖﺳا هدﺮﮐ ﺮﯿﯿﻐﺗ شﻮﺨﺘﺳد ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ رد ار

ﯽﺑﺎــﻨﺘﺟا يﺮﯿﮔدﺎــﯾ رﺎــﺘﻓر ﺢﻄــﺳ رد ﺎــﻣ ﻪﻌﻟﺎﻄﻣ ﺞﯾﺎﺘﻧ ﻨﻌﻣ تاﺮﺛا ناﺪﻧزﺮﻓ ﯽ

ﺎــﺑ ﺎــﻣا داﺪــﻧ نﺎﺸﻧ تاوﺮﭙﻟاو زا يراد

اﺪﻘﻓ ﻪﺑ ﻪﺟﻮﺗ ﺖﯾوﺪــﺤﻣ و ﻪﻨﯿﻣز ﻦﯾا رد ﺮﮕﯾد تﺎﻌﻟﺎﻄﻣ ن

يﺎﻫ

ﺮﯾﺎــﺳ ﺶﺠﻨــﺳ ﻪــﺑ زﺎــﯿﻧ قﻮﻓ ﻪﯿﺿﺮﻓ لﻮﺒﻗ ﺎﯾ در ،ﺎﻣ ﻪﻌﻟﺎﻄﻣ نﺎــﯿﺑ ﯽــﺳرﺮﺑ رد ﺎــﻣ ﺞﯾﺎﺘﻧ ﻪﮐ صﻮﺼﺧ ﻪﺑ ،دراد يرﺎﺘﻓر دﺎﻌﺑا نژ ناﺪــﻧزﺮﻓ ﻪــﮐ داد نﺎــﺸﻧ ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ ﻪﯿﺣﺎﻧ يﺎﻫ رد ار ﯽﺗوﺎــﻔﺘﻣ ﯽــﻧژ نﺎــﯿﺑ يﻮــﮕﻟا ،تاوﺮﭙﻟاو ناردﺎﻣ هدﺎﻣ

ﺎﺑ ﻪﺴﯾﺎﻘﻣ ﺮــﻈﻧ ﻪــﺑ ﻦﯾاﺮﺑﺎــﻨﺑ .ﺪــﻧراد لﺮــﺘﻨﮐ هدﺎــﻣ ناﺪــﻧزﺮﻓ

ﯽﻣ ﻞﺑﺎﻗ تاوﺮﭙﻟاو ﯽﻠﺴﻧ ﻦﯿﺑ تاﺮﺛا نژ نﺎﯿﺑ ﺢﻄﺳ رد ﺪﺳر ﻪــﻌﻟﺎﻄﻣ رد ﯽــﺳرﺮﺑ درﻮــﻣ نژ ﻪﺳ درﻮﻣ رد و ﺖﺳا ﯽﺑﺎﯾدر

ﯽﻣ زوﺮﺑ ﺲﻨﺟ ﻪﺑ ﻪﺘﺴﺑاو ترﻮﺻ ﻪﺑ تاﺮﺛا ﻦﯾا ﺎﻣ ﺎــﺑ .ﺪﻨﻨﮐ

نژ يﺮــﺳ زا نژ ﻪــﺳ ﺮــﻫ ﻪــﮐ ﻦــﯾا ﻪﺑ ﻪﺟﻮﺗ ﯽــﻤﯿﻈﻨﺗ يﺎــﻫ

ﯽﻣ ﺘﻨﮐ رد و ﺪﻨﺷﺎﺑ نژ ﺮﯾﺎﺳ لﺮ

يﺎﻫﺪــﻨﯾاﺮﻓ رد ﻞــﯿﺧد يﺎﻫ

ﻪﺑ ﯽﻟﻮﻠﺳ ﯽﻣ ،ﺪﻧراد ﺶﻘﻧ ﯽﺒﺼﻋ ﻢﺘﺴﯿﺳ رد صﻮﺼﺧ ناﻮﺗ

.ﺪﻨﻫد ﺮﯿﯿﻐﺗ ﺰﯿﻧ ار ﯽﺒﺼﻋ ﻢﺘﺴﯿﺳ يﺎﻫدﺮﮐرﺎﮐ ﺖﺷاد رﺎﻈﺘﻧا ﯽــﺳرﺮﺑ و نژ نﺎــﯿﺑ ﯽــﺳرﺮﺑ رد ﺎــﻣ ﺞﯾﺎــﺘﻧ ﻦﯿــﺑ لﺎﺣ ﻦﯾا ﺎﺑ مﺪــﻋ ﻦــﯾا ﻞــﯿﻟد ﮏــﯾ .ﺪــﺸﻧ هﺪﻫﺎــﺸﻣ ﯽﻧاﻮــﺨﻤﻫ يرﺎﺘﻓر ﯽﻣ ﯽﻧاﻮﺨﻤﻫ ﻓر نﻮﻣزآ عﻮﻧ رد ﺪﻧاﻮﺗ

ﺖﯾدوﺪــﺤﻣ و يرﺎــﺘ

ﯽﻣ ﺮﮕﯾد ﻞﯿﻟد .ﺪﺷﺎﺑ نآ زا جاﺮﺨﺘﺳا ﻞﺑﺎﻗ تﺎﻋﻼﻃا ﺪﻧاﻮﺗ

.ددﺮــﮔﺮﺑ ﻢﺘــﺴﯿﺳ يﺎﻫدﺮﮐرﺎﮐ ﺮﺑ ﻂﯿﺤﻣ تاﺮﺛا و نﺎﻣز ﻪﺑ نﺎﻤﻫ ،ﯽﺗرﺎﺒﻋ ﻪﺑ ،ﺪــﺷ ﻪﺘــﺷﻮﻧ رﺎﮐ شور ﺶﺨﺑ رد ﻪﮐرﻮﻃ

يراﻮﺧﺮﯿــﺷ هرود ﯽــﻃ زا ﺪﻌﺑ ناﺪﻧزﺮﻓ رد يرﺎﺘﻓر ﯽﺳرﺮﺑ ــﯿﯿﻐﺗ ﺮــﺑ ﻂﯿــﺤﻣ تاﺮﺛا و ﯽﻧﺎﻣز ﻪﻠﺻﺎﻓ ﻦﯾا .ﺪﺷ مﺎﺠﻧا تاﺮ

ﯽﭘا فﺎﻄﻌﻧا ﻪﺑ ﻪﺟﻮﺗ ﺎﺑ ﮏﯿﺘﻧژ و تاﺮــﯿﯿﻐﺗ ﻦــﯾا ندﻮﺑ ﺮﯾﺬﭘ

ندﻮﺑ ﺮﺛﺎﺘﻣ ﯽﻣ ﻂﯿﺤﻣ ﻂﯾاﺮﺷ زا نﺎﺷ تاﺮﯿﯿﻐﺗ ﯽﺧﺮﺑ ﺪﻨﻧاﻮﺗ

نﺎــﺸﻧ ﻪﻌﻟﺎﻄﻣ ﮏﯾ ﺎﺘﺳار ﻦﯿﻤﻫ رد .ﺪﻨﮐ ناﺮﺒﺟ ار ﯽﻟﺎﻤﺘﺣا ﻢﺘــﺴﯿﺳ يﺎــﻫدﺮﮐرﺎﮐ ﺮــﺑ تاوﺮــﭙﻟاو تاﺮﺛا زا ﯽﺧﺮﺑ هداد نﺎــﻣز ﻪــﺑ ﻪﺘﺴﺑاو ترﻮﺻ ﻪﺑ نآ زا ﯽﺷﺎﻧ تاﺮﯿﯿﻐﺗ و ﯽﺒﺼﻋ ﺑ ﺖﺸﮔﺮ ﺖﺳا ﺮﯾﺬﭘ ) 18 (.

ﯽــﭘا تاﺮــﺛا ﻪــﯾﺎﭘ ﺮــﺑ ﺐــﻟﺎﺟ ﻪــﻌﻟﺎﻄﻣ ﮏــﯾ ﮏــﯿﺘﻧژ

داد نﺎــﺸﻧ تاﺮﺛا ﻦﯾا ﯽﻠﺴﻧ ﻦﯿﺑ لﺎﻘﺘﻧا لﺎﻤﺘﺣا و تاوﺮﭙﻟاو ﺪﻧزﺮﻓ ﻪﮐ تاوﺮﭙﻟاو ﺎﺑ ﻪﻬﺟاﻮﻣ رد ﯽﻨﯿﻨﺟ هرود ﯽﻃ ﻪﮐ ﯽﻧا

ﻪﺘــﺷاد راﺮــﻗ نﺎــﺸﻧ ار ﻢــﺴﯿﺗوا ﻪﺒــﺷ لﻼﺘــﺧا ﺎــﻬﻨﺗ ﻪــﻧ ،ﺪﻧا

ﯽﻣ ﻞــﻘﺘﻨﻣ دﻮــﺧ يﺪــﻌﺑ ﻞﺴﻧ ﻪﺑ ار لﻼﺘﺧا ﻦﯾا ﻪﮑﻠﺑ ،ﺪﻨﻫد

ﯽﻣ ﺪﻨﻨﮐ ) 16 ﺮﮕﻧﺎﯿﺑ ﺞﯾﺎﺘﻧ ﻦﯾا (.

ﯽﭘا ﺖﺛارو ﮏﯿﺘﻧژ

لﺎﻘﺘﻧا و

.ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ ﯽﻤﯿﻈﻨﺗيﺎﻫ نژ نﺎﯿﺑ ﺮﺑ يرادرﺎﺑ زا ﻞﺒﻗ تاوﺮﭙﻟاو فﺮﺼﻣ ﺮﺛا2. هرﺎﻤﺷ رادﻮﻤﻧ

رد تاوﺮﭙﻟاو هدﺎﻣ ناﺪﻧزﺮﻓ ﭗﻤﮐﻮﭙﯿﻫ رد نژ ﻪﺳ ﺮﻫ نﺎﯿﺑ

ﻌﻣ ﺶﻫﺎﮐ لﺮﺘﻨﮐ هدﺎﻣ ناﺪﻧزﺮﻓ ﺎﺑ ﻪﺴﯾﺎﻘﻣ ) ﺪﻫد ﯽﻣ نﺎﺸﻧ ار يراد ﯽﻨ

01 /0

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(P

ترﻮﺻ ﻪﺑ ﺎﻫ هداد. mean±SEM

ﻪﺋارا ﺮﮕﻧﺎﯿﺑ ** .ﺪﻧا هﺪﺷ 01

/0

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ردP

) لﺮﺘﻨﮐ يﺎﻫ هدﺎﻣ ﺎﺑ ﻪﺴﯾﺎﻘﻣ

female cnt

( ﺎﻫ هوﺮﮔ ﻪﻤﻫ ياﺮﺑ .ﺖﺳا 6

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(6)

ﻦﯿﺑ ﯽﻠﺴﻧ ﯽﻣ تاوﺮﭙﻟاو تاﺮﺛا ﯽﻣ نﺎﺸﻧ و ﺪﺷﺎﺑ

سﺎﻤﺗ ﺪﻫد

لﻮﻠﺳ ﯿــﭘ تاوﺮﭙﻟاو ﺎﺑ هدﺎﻣ ﯽﺴﻨﺟ يﺎﻫ ﻞﯿﮑــﺸﺗ و حﺎــﻘﻟ زا ﺶ

ﻞﺴﻧ رد ناﺪﻧزﺮﻓ ﭗﯿﺗﻮﻨﻓ ﺮﺑ ،ﻦﯿﻨﺟ .ﺖﺳا راﺬﮔﺮﺛا يﺪﻌﺑ يﺎﻫ

يراﺰﮕﺳﺎﭙﺳ

بﻮــﺼﻣ ﯽﺗﺎــﻘﯿﻘﺤﺗ حﺮــﻃ زا ﻪــﺘﻓﺮﮔﺮﺑ ﻪــﻌﻟﺎﻄﻣ ﻦــﯾا ياﺮﺑ ﯽﻌﻓﺎﻨﻣ دﺎﻀﺗ .ﺪﺷﺎﺑ ﯽﻣ كارا ﯽﮑﺷﺰﭘ مﻮﻠﻋ هﺎﮕﺸﻧاد

.دراﺪﻧ دﻮﺟو نﺎﮔﺪﻨﺴﯾﻮﻧ

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8. Federman N, Zalcman G, de la Fuente V, Fustinana MS,Romano A. Epigenetic mechanisms

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