Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.
Inhibition of soluble tumor necrosis factor ameliorates synaptic alterations and Ca2+ dysregulation in aged rats.
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DOI：
10.1371/journal.pone.0038170
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Norris CM
中科院分区：
文献类型：
--
作者：
Sama DM;Mohmmad Abdul H;Furman JL;Artiushin IA;Szymkowski DE;Scheff SW;Norris CM
肿瘤坏死因子α (TNF)在神经功能中的作用已经在几种神经退行性疾病中得到了广泛的研究，但很少在脑衰老中进行研究，其中认知和生理变化更温和且更多变。在这里，我们发现在年龄（22个月）的Fischer 344大鼠中，海马中TNF受体1 （TNFR1）的蛋白水平明显高于TNF受体2 (TNFR2)，而不是年轻成年（6个月）的大鼠。为了确定改变的TNF/TNFR1相互作用是否有助于关键的脑老化生物标志物，老龄大鼠接受慢性（4-6周）颅内输注XPro1595：一种可溶性显性阴性TNF，优先抑制TNFR1信号。用XPro1595治疗的老年大鼠表现出Morris水迷宫表现改善，小胶质细胞激活降低，海马长期抑郁易感性降低，GluR1型谷氨酸受体蛋白水平升高，海马CA1神经元l型电压敏感Ca2+通道（VSCC）活性降低。结果表明，与脑衰老相关的各种功能变化可能部分来自TNF信号的选择性改变。
The role of tumor necrosis factor α (TNF) in neural function has been investigated extensively in several neurodegenerative conditions, but rarely in brain aging, where cognitive and physiologic changes are milder and more variable. Here, we show that protein levels for TNF receptor 1 (TNFR1) are significantly elevated in the hippocampus relative to TNF receptor 2 (TNFR2) in aged (22 months) but not young adult (6 months) Fischer 344 rats. To determine if altered TNF/TNFR1 interactions contribute to key brain aging biomarkers, aged rats received chronic (4–6 week) intracranial infusions of XPro1595: a soluble dominant negative TNF that preferentially inhibits TNFR1 signaling. Aged rats treated with XPro1595 showed improved Morris Water Maze performance, reduced microglial activation, reduced susceptibility to hippocampal long-term depression, increased protein levels for the GluR1 type glutamate receptor, and lower L-type voltage sensitive Ca2+ channel (VSCC) activity in hippocampal CA1 neurons. The results suggest that diverse functional changes associated with brain aging may arise, in part, from selective alterations in TNF signaling.
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影响因子：
2.2
作者：
Blalock, EM;Chen, KC;Slevin, JT
通讯作者：
Slevin, JT
DOI：
10.1073/pnas.89.10.4363
发表时间：
1992-05-15
影响因子：
11.1
作者：
DUDEK, SM;BEAR, MF
通讯作者：
BEAR, MF
DOI：
10.1073/pnas.2236970100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Davare, MA;Hell, JW
通讯作者：
Hell, JW
影响因子：
3.8
作者：
Aloe, L;Fiore, M;Tirassa, P
通讯作者：
Tirassa, P
影响因子：
56.9
作者：
Beattie, EC;Stellwagen, D;Malenka, RC
通讯作者：
Malenka, RC