Nigral GFRα1 infusion in aged rats increases locomotor activity, nigral tyrosine hydroxylase, and dopamine content in synchronicity.
Nigral GFRα1 infusion in aged rats increases locomotor activity, nigral tyrosine hydroxylase, and dopamine content in synchronicity.
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DOI：
10.1007/s12035-013-8397-7
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发表时间：
2013-06
影响因子：
5.1
通讯作者：
Salvatore, Michael F.
中科院分区：
文献类型：
--
作者：
Pruett, Brandon S.;Salvatore, Michael F.
外源性胶质细胞源性神经营养因子（GDNF）的递送增加了衰老和帕金森病的啮齿动物模型中的运动活性，同时增加了黑质（SN）中的多巴胺（DA）组织含量。纹状体GDNF输注也增加了老年大鼠SN中GDNF同源受体GFRα1和酪氨酸羟化酶（TH）ser31磷酸化的表达，在GDNF升高后很长时间内不再检测到。在衰老过程中，SN中可溶性GFRα1的表达降低，与TH表达、TH ser31磷酸化、DA组织含量和运动活性降低相关。因此，我们假设，在老年大鼠中，补充SN中的可溶性GFRα1可以逆转这些缺陷并增加运动活性。我们测定了年轻成年大鼠SN中可溶性GFRα1的量约为3.6 ng。为了补充年龄相关的损失（约30%），我们将1 ng可溶性GFRα1双侧输注到老年雄性大鼠的SN中，并观察到与输注溶剂的大鼠相比，输注后长达4天的自发活动增加，第3天的作用最大。然而，输注后5天，两组之间的自发活动和黑质纹状体神经化学指标均无显著差异。在一个单独的雄性大鼠队列中，在SN中单侧输注1 ng可溶性GFRα 1后3天，黑质（而非纹状体）DA、TH和THser31磷酸化水平升高。因此，在老年雄性大鼠中，通过补充与年龄相关的可溶性GFRα 1损失诱导的自发活动的短暂增加与黑质多巴胺能功能的增加在时间上相匹配。因此，可溶性GFRα1在SN中的表达可能是通过其对TH调节和DA生物合成的影响来调节运动活性的关键组分。
Delivery of exogenous glial cell line-derived neurotrophic factor (GDNF) increases locomotor activity in rodent models of aging and Parkinson’s disease in conjunction with increased dopamine (DA) tissue content in substantia nigra (SN). Striatal GDNF infusion also increases expression of GDNF’s cognate receptor, GFRα1, and tyrosine hydroxylase (TH) ser31 phosphorylation in the SN of aged rats long after elevated GDNF is no longer detectable. In aging, expression of soluble GFRα1 in the SN decreases in association with decreased TH expression, TH ser31 phosphorylation, DA tissue content, and locomotor activity. Thus, we hypothesized that, in aged rats, replenishing soluble GFRα1 in SN could reverse these deficits and increase locomotor activity. We determined that the quantity of soluble GFRα1 in young adult rat SN is ~3.6 ng. To replenish age-related loss, which is ~30 %, we infused 1 ng soluble GFRα1 bilaterally into SN of aged male rats and observed increased locomotor activity compared to vehicle-infused rats up to 4 days following infusion, with maximal effects on day 3. Five days after infusion, however, neither locomotor activity nor nigrostriatal neurochemical measures were significantly different between groups. In a separate cohort of male rats, nigral, but not striatal, DA, TH, and THser31 phosphorylation were increased 3 days following unilateral infusion of 1 ng soluble GFRα1into SN. Therefore, in aged male rats, the transient increase in locomotor activity induced by replenishing age-related loss of soluble GFRα1is temporally matched with increased nigral dopaminergic function. Thus, expression of soluble GFRα1 in SN may be a key component in locomotor activity regulation through its influence over TH regulation and DA biosynthesis.
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影响因子：
2.9
作者：
Bergquist, F;Shahabi, HN;Nissbrandt, H
通讯作者：
Nissbrandt, H
DOI：
10.1073/pnas.89.6.2365
发表时间：
1992-03-15
影响因子：
11.1
作者：
HAYCOCK, JW;AHN, NG;KREBS, EG
通讯作者：
KREBS, EG
影响因子：
2.9
作者：
Aoi, M;Date, I;Ohmoto, T
通讯作者：
Ohmoto, T
影响因子：
82.9
作者：
Gill, SS;Patel, NK;Heywood, P
通讯作者：
Heywood, P
影响因子：
3.4
作者：
Andersson, Daniel R.;Nissbrandt, Hans;Bergquist, Filip
通讯作者：
Bergquist, Filip