اثر محافظتی تجویز داخل بینی انسولین بر عملکردهای شناختی و نوروژنز در موش صحرایی مدل بیماری آلزایمر

ﺳﺎﺑﻘﻪ و ﻫﺪف: ﺑﯿﻤﺎری آﻟﺰاﯾﻤﺮ ﺷﺎﯾﻊﺗﺮﯾﻦ ﺑﯿﻤﺎری ﻣﺨﺮب ﻣﻐﺰی اﺳﺖ ﮐﻪ ﺑﺎ اﺧﺘﻼﻻت ﺷﻨﺎﺧﺘﯽ ﻫﻤﺮاه ﻣﯽﺑﺎﺷﺪ. ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻧﻘﺶ ﻣﺤﺎﻓﻈﺘﯽ اﻧﺴﻮﻟﯿﻦ در ﻋﻤﻠﮑﺮدﻫﺎی ﺳﯿﺴﺘﻢ ﻋﺼﺒﯽ، ﻫﺪف از ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ ﺑﺮرﺳﯽ اﺛﺮ ﺗﺠﻮﯾﺰ داﺧﻞ ﺑﯿﻨﯽ اﻧﺴﻮﻟﯿﻦ ﺑﺮ اﺧﺘﻼﻻت ﺷﻨﺎﺧﺘﯽ و ﻧﻮروژﻧﺰ در ﻣﻮشﻫﺎی ﺻﺤﺮاﯾﯽ ﺗﯿﻤﺎر ﺷﺪه ﺑﺎ اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ stz ﻣﯽﺑﺎﺷﺪ. ﻣﻮاد و روشﻫﺎ: در اﯾﻦ ﻣﻄﺎﻟﻌﻪ ﺗﺠﺮﺑﯽ 32 ﺳﺮ ﻣﻮش ﺻﺤﺮاﯾﯽ ﻧﺮ ﻧﮋاد وﯾﺴﺘﺎر در 4 ﮔﺮوه 8 ﺗﺎﯾﯽ: ﮐﻨﺘﺮل، stz ،stz+اﻧﺴﻮﻟﯿﻦ و اﻧﺴﻮﻟﯿﻦ ﺗﻘﺴﯿﻢ ﺑﻨﺪی ﺷﺪﻧﺪ. ﻣﺪل آﻟﺰاﯾﻤﺮ ﺑﺎ ﺗﺰرﯾﻖ درون ﺑﻄﻨﯽmg/kg stz 3 ؛ μl 3 در ﻫﺮ ﺑﻄﻦ اﻟﻘﺎء ﺷﺪ. دو ﻫﻔﺘﻪ ﭘﺲ از ﺗﺰرﯾﻖ stz، ﺑﺮرﺳﯽ ﻋﻤﻠﮑﺮدﻫﺎی ﺷﻨﺎﺧﺘﯽ ﺑﺎ اﺳﺘﻔﺎده از ﺗﺴﺖ ﻣﺎز ﺑﻌﻼوهای ﺷﮑﻞ ﻣﺮﺗﻔﻊ elevated plus maze= epm و آزﻣﻮن ﯾﺎدﮔﯿﺮی اﺟﺘﻨﺎﺑﯽ ﻏﯿﺮﻓﻌﺎل passive avoidance= pa اﻧﺠﺎم ﮔﺮﻓﺖ. ﺗﯿﻤﺎر ﺑﺎ اﻧﺴﻮﻟﯿﻦ روزاﻧﻪ iu 2؛ μl 10 در ﻫﺮ ﻣﺠﺮای ﺑﯿﻨﯽ ﭘﺲ از ﺗﺰرﯾﻖ stz و ﺑﻪ ﻣﺪت 14 روز ﻣﺘﻮاﻟﯽ اﻧﺠﺎم ﮔﺮﻓﺖ. ﺗﻐﯿﯿﺮ ﺑﯿﺎن ژنﻫﺎی دﺧﯿﻞ در ﻧﻮروژﻧﺰ dcx ،nestin وki67 در ﻧﺎﺣﯿﻪ ﻫﯿﭙﻮﮐﺎﻣﭗ، ﺗﻮﺳﻂ ﺗﮑﻨﯿﮏreal-time pcr ﺑﺮرﺳﯽ ﮔﺮدﯾﺪ. ﯾﺎﻓﺘﻪﻫﺎ: stz ﺳﺒﺐ اﻓﺰاﯾﺶ ﺣﻀﻮر در ﺑﺎزوﻫﺎی ﺑﺎز در ﻣﺮﺣﻠﻪ اﮐﺘﺴﺎب 64/5±5/24 و ﺑﻪ ﯾﺎدآوری ﺣﺎﻓﻈﻪ 60/25±5/55 ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﮐﻨﺘﺮل 33±2/17 و 26/38±2/06 در ﺗﺴﺖ epm ﺷﺪ ﺑﻪ ﺗﺮﺗﯿﺐ p<0/05 و p<0/01 . ﺑﻌﻼوه ﺳﺒﺐ ﮐﺎﻫﺶ ﺑﻪ ﺧﺎﻃﺮآوری ﯾﺎدﮔﯿﺮی 90 دﻗﯿﻘﻪ 6/03±77/57 و 24 ساعت 7/25±90/25 بعد از آموزش، نسبت به گروه کنترل 3/19±254/38 و 3/46±238/13 در تست pa شد ﺑﻪ ﺗﺮﺗﯿﺐ p<0/001 و p<0/05 . ﺗﯿﻤﺎر ﺑﺎ اﻧﺴﻮﻟﯿﻦ ﺳﺒﺐ ﺑﻬﺒﻮد ﭘﺎراﻣﺘﺮﻫﺎی ﻓﻮق در ﺗﺴﺖ epm ﺑﻪ ﺗﺮﺗﯿﺐ 41/88±4/14 و 31/5±4/16 و pa ﺑﻪ ﺗﺮﺗﯿﺐ 278/88±2/32 و 218/5±2/12 ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه stz ﺷﺪ. stz ﻫﻤﭽﻨﯿﻦ ﻣﻨﺠﺮ ﺑﻪ ﮐﺎﻫﺶ ﺑﯿﺎن ژن nestin 0/46±0/04 ، dcx 0/35±0/04 وki67 0/41±0/05 ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﮐﻨﺘﺮل ﺑﻪ ﺗﺮﺗﯿﺐ 1±0/04 ،1/02±0/11 و 1/01±0/08 ﮔﺮدﯾﺪ ﺑﻪ ﺗﺮﺗﯿﺐ p<0/001 ،p<0/01 و p<0/001 ، در ﺣﺎﻟﯽ ﮐﻪ ﺗﯿﻤﺎر ﺑﺎ اﻧﺴﻮﻟﯿﻦ ﺗﻮاﻧﺴﺖ ﺑﯿﺎن اﯾﻦ ژنﻫﺎ را اﻓﺰاﯾﺶ دﻫﺪ ﺑﻪ ﺗﺮﺗﯿﺐ 0/87±0/09، 0/78±0/02 و p<0/05 0/69±0/08 . ﻧﺘﯿﺠﻪﮔﯿﺮی: ﻧﺘﺎﯾﺞ ﻧﺸﺎن داد ﮐﻪ اﻧﺴﻮﻟﯿﻦ ﺳﺒﺐ ﺑﻬﺒﻮد ﻋﻤﻠﮑﺮدﻫﺎی ﺷﻨﺎﺧﺘﯽ و اﻓﺰاﯾﺶ ﻧﻮروژﻧﺰ در ﻣﻮشﻫﺎی ﺗﯿﻤﺎر ﺷﺪه ﺑﺎ stz ﮔﺮدﯾﺪ، ﺑﻨﺎﺑﺮاﯾﻦ اﻧﺴﻮﻟﯿﻦ ﻣﯽﺗﻮاﻧﺪ ﺑﻪ ﻋﻨﻮان ﯾﮏ ﻫﺪف درﻣﺎﻧﯽ ﻣﻮﺛﺮ در ﺑﯿﻤﺎری آﻟﺰاﯾﻤﺮ ﻣﻮرد ﺗﻮﺟﻪ ﺑﯿﺸﺘﺮی ﻗﺮار ﺑﮕﯿﺮد.

protective effect of intranasal insulin administration on cognitive functions and neurogenesis in a rat model of alzheimer's disease

background and objective: alzheimer’s disease is the most common destructive brain disease which is associated with cognitive disorders. considering the protective role of insulin in the functions of the nervous system, the present study was conducted to investigate the effect of intranasal insulin administration on cognitive disorders and neurogenesis in rats treated with streptozotocin stz .methods: in this experimental study, 32 male wistar rats were divided into 4 groups of 8: control, stz, stz + insulin and insulin. the model of alzheimer’s disease was induced by intraventricular injection of stz 3 mg/kg; 3 μl in each ventricle . two weeks after stz injection, cognitive functions were evaluated using elevated plus maze epm and passive avoidance pa tests. insulin treatment 2 iu daily; 10 μl in each nasal passage was performed after stz injection for 14 consecutive days. the change in the expression of genes involved in neurogenesis nestin, dcx and ki67 in the hippocampus area was investigated by real-time pcr technique.findings: stz caused longer animal stay in open arms in acquisition phase 64.5±5.24 and recall phase 60.25±5.55 compared to the control group 33±2.17 and 26.38±2.06 in the epm test p<0.05 and p<0.01, respectively . in addition, it caused a decrease in learning recall 90 minutes 77.57±6.03 and 24 hours 90.25±7.25 after training, compared to the control group 254.38±3.19 and 238.13±3.46 in the pa test p<0.001 and p<0.05, respectively . insulin treatment improved the above parameters in epm test 41.88±4.14 and 31.5±4.16, respectively and pa 278.88±2.32 and 218.5±2.12, respectively compared to the stz group. stz also led to a decrease in nestin gene expression 0.46±0.04 , dcx 0.35±0.04 and ki67 0.41±0.05 compared to the control group 1.02±0.11, 1±0.04 and 1.01±0.08, respectively p<0.01, p<0.001 and p<0.001, respectively , while insulin treatment could increase the expression of these genes 0.87±0.09, 0.78±0.02 and 0.69±0.08, respectively p<0.05 .conclusion: the results showed that insulin improved cognitive functions and increased neurogenesis in rats treated with stz. therefore, insulin can be considered as an effective therapeutic target in alzheimer’s disease.