語系:
繁體中文
English
說明(常見問題)
回圖書館首頁
手機版館藏查詢
登入
回首頁
到查詢結果
[ subject:"Biology, Neurobiology." ]
切換:
標籤
|
MARC模式
|
ISBD
The role of microglia in morphine to...
~
Horvath, Ryan Joseph.
FindBook
Google Book
Amazon
博客來
The role of microglia in morphine tolerance.
紀錄類型:
書目-語言資料,印刷品 : Monograph/item
正題名/作者:
The role of microglia in morphine tolerance./
作者:
Horvath, Ryan Joseph.
面頁冊數:
272 p.
附註:
Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3491.
Contained By:
Dissertation Abstracts International71-06B.
標題:
Biology, Neurobiology. -
電子資源:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3404441
ISBN:
9781124014838
The role of microglia in morphine tolerance.
Horvath, Ryan Joseph.
The role of microglia in morphine tolerance.
- 272 p.
Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3491.
Thesis (Ph.D.)--Dartmouth College, 2010.
Chronic pain is a debilitating condition which exacts severe emotional, physical and economic tolls on the millions of people who suffer from it worldwide. Opioids are a mainstay of acute, postoperative and cancer pain therapy, however, their use for the treatment of chronic pain is limited by side effects including analgesic tolerance. Although the mechanisms driving analgesic tolerance are not fully understood, we propose that spinal cord glial cells have a fundamental role in this phenomenon. We hypothesize that acutely, morphine binds to abundant neuronal mu opioid receptors, producing analgesia. Chronically, morphine binds to less abundant microglial mu opioid receptors, enhancing intracellular pathway signaling, protein expression and cell migration, causing proinflammatory factor mediated neuronal sensitization and ultimately analgesic tolerance. In Chapter 3, we demonstrated that in vitro ADP dependent microglial migration can be inhibited by glial modulating agents. In Chapter 4, we showed that in vitro morphine treatment enhanced mu opioid receptor dependent microglial migration towards ADP via P2X4 receptor activation and PI3K/Akt signaling. In Chapter 5, we showed that antisense oligonucleotide-mediated inhibition of microglial P2X 4 receptor expression attenuated the development of morphine tolerance in vivo. In Chapter 6, we showed that morphine tolerance attenuated the resolution of postoperative allodynia and enhanced microglial p38 and ERK phosphorylation in vivo. In Chapter 7, we explored the mechanism of morphine-induced microglial migration. We showed that in vitro morphine treatment enhances cytosolic beta-catenin expression in microglia and that microglial migration is enhanced towards organotypic spinal cord slices harvested from animals treated in vivo or ex vivo with morphine. This thesis describes the following major contributions to the opioid tolerance field: (1) Identification of cellular migration as a significant functional response of microglia to morphine stimulation; (2) Identification of the modulatory role of microglial P2X4 receptors in the development of morphine tolerance; (3) Introduction of the idea that prior morphine tolerance can prime microglia to respond more robustly to subsequent stimuli; (4) Development of the ex vivo organotypic slice culture technique to allow for the evaluation of the molecular and cellular changes associated with microglial migration and chemoattractant production in morphine tolerant states.
ISBN: 9781124014838Subjects--Topical Terms:
1681328
Biology, Neurobiology.
The role of microglia in morphine tolerance.
LDR
:03530nam 2200313 4500
001
1404546
005
20111130124033.5
008
130515s2010 ||||||||||||||||| ||eng d
020
$a
9781124014838
035
$a
(UMI)AAI3404441
035
$a
AAI3404441
040
$a
UMI
$c
UMI
100
1
$a
Horvath, Ryan Joseph.
$3
1683874
245
1 4
$a
The role of microglia in morphine tolerance.
300
$a
272 p.
500
$a
Source: Dissertation Abstracts International, Volume: 71-06, Section: B, page: 3491.
500
$a
Adviser: Joyce A. DeLeo.
502
$a
Thesis (Ph.D.)--Dartmouth College, 2010.
520
$a
Chronic pain is a debilitating condition which exacts severe emotional, physical and economic tolls on the millions of people who suffer from it worldwide. Opioids are a mainstay of acute, postoperative and cancer pain therapy, however, their use for the treatment of chronic pain is limited by side effects including analgesic tolerance. Although the mechanisms driving analgesic tolerance are not fully understood, we propose that spinal cord glial cells have a fundamental role in this phenomenon. We hypothesize that acutely, morphine binds to abundant neuronal mu opioid receptors, producing analgesia. Chronically, morphine binds to less abundant microglial mu opioid receptors, enhancing intracellular pathway signaling, protein expression and cell migration, causing proinflammatory factor mediated neuronal sensitization and ultimately analgesic tolerance. In Chapter 3, we demonstrated that in vitro ADP dependent microglial migration can be inhibited by glial modulating agents. In Chapter 4, we showed that in vitro morphine treatment enhanced mu opioid receptor dependent microglial migration towards ADP via P2X4 receptor activation and PI3K/Akt signaling. In Chapter 5, we showed that antisense oligonucleotide-mediated inhibition of microglial P2X 4 receptor expression attenuated the development of morphine tolerance in vivo. In Chapter 6, we showed that morphine tolerance attenuated the resolution of postoperative allodynia and enhanced microglial p38 and ERK phosphorylation in vivo. In Chapter 7, we explored the mechanism of morphine-induced microglial migration. We showed that in vitro morphine treatment enhances cytosolic beta-catenin expression in microglia and that microglial migration is enhanced towards organotypic spinal cord slices harvested from animals treated in vivo or ex vivo with morphine. This thesis describes the following major contributions to the opioid tolerance field: (1) Identification of cellular migration as a significant functional response of microglia to morphine stimulation; (2) Identification of the modulatory role of microglial P2X4 receptors in the development of morphine tolerance; (3) Introduction of the idea that prior morphine tolerance can prime microglia to respond more robustly to subsequent stimuli; (4) Development of the ex vivo organotypic slice culture technique to allow for the evaluation of the molecular and cellular changes associated with microglial migration and chemoattractant production in morphine tolerant states.
590
$a
School code: 0059.
650
4
$a
Biology, Neurobiology.
$3
1681328
690
$a
0421
710
2
$a
Dartmouth College.
$b
Pharmacology and Toxicology.
$3
1683875
773
0
$t
Dissertation Abstracts International
$g
71-06B.
790
1 0
$a
DeLeo, Joyce A.,
$e
advisor
790
1 0
$a
Harris, Brent T.
$e
committee member
790
1 0
$a
Hwa, John
$e
committee member
790
1 0
$a
Ji, Ru-Rong
$e
committee member
790
1 0
$a
Martin, Kathleen A.
$e
committee member
790
$a
0059
791
$a
Ph.D.
792
$a
2010
856
4 0
$u
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3404441
筆 0 讀者評論
館藏地:
全部
電子資源
出版年:
卷號:
館藏
1 筆 • 頁數 1 •
1
條碼號
典藏地名稱
館藏流通類別
資料類型
索書號
使用類型
借閱狀態
預約狀態
備註欄
附件
W9167685
電子資源
11.線上閱覽_V
電子書
EB
一般使用(Normal)
在架
0
1 筆 • 頁數 1 •
1
多媒體
評論
新增評論
分享你的心得
Export
取書館
處理中
...
變更密碼
登入