Tricyclic antidepressant treatment evokes regional changes in neurotrophic factors over time within the intact and degenerating nigrostriatal system.
Tricyclic antidepressant treatment evokes regional changes in neurotrophic factors over time within the intact and degenerating nigrostriatal system.
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DOI：
10.1016/j.expneurol.2015.02.005
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发表时间：
2015-04
影响因子：
5.3
通讯作者：
Collier, Timothy J.
中科院分区：
文献类型：
--
作者：
Paumier, Katrina L.;Sortvvell, Caryl E.;Madhavan, Lalitha;Terpstra, Brian;Daley, Brian F.;Collier, Timothy J.
除了缓解抑郁症外，抗抑郁药产生的营养反应还可以调节患病大脑的神经可塑性，不仅提供症状益处，还可能减缓帕金森病（PD）的疾病进展速度。最近的体外和体内数据提供的证据表明，神经营养因子，如脑源性神经营养因子（BDNF）和胶质细胞系源性神经营养因子（GDNF）可能是抗抑郁药治疗反应的关键介质。因此，我们进行了一项横断面时间过程研究，以确定是否抗抑郁药介导的神经营养因子的变化发生在相关的脑区域，以应对阿米替林（AMI）治疗前和纹状体内6-羟基多巴胺（6 OHDA）。将成年雄性Wistar大鼠分成7个群组，每天注射（i. p.）AMI（5 mg/kg）或生理盐水。同时，在特定时间点处死不同队列的完整或帕金森病动物，以确定AMI治疗对完整和退化黑质纹状体系统中营养因子水平的影响。采用酶联免疫吸附法（ELISA）检测各组大鼠大脑左右半球黑质、纹状体、额叶皮质、梨状皮质、海马和前扣带回皮质的BDNF和GDNF水平。结果表明，慢性AMI治疗在多个脑区发挥作用，并根据区域差异调节BDNF和GDNF水平。此外，AMI阻止了纹状体内6-OHDA损伤引起的多巴胺（DA）神经元的进行性变性。总而言之，这些结果表明AMI治疗引起了显着的营养变化，这对完整和退化的黑质纹状体系统内的DA神经元存活很重要。
In addition to alleviating depression, trophic responses produced by antidepressants may regulate neural plasticity in the diseased brain, providing not only symptomatic benefit but potentially slowing the rate of disease progression in Parkinson’s disease (PD). Recent in vitro and in vivo data provide evidence that neurotrophic factors such as brain derived-neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) may be key mediators of the therapeutic response to antidepressants. As such, we conducted a cross-sectional time-course study to determine whether antidepressant-mediated changes in neurotrophic factors occur in relevant brain regions in response to amitriptyline (AMI) treatment before and after intrastriatal 6-hydroxydopamine (6OHDA). Adult male Wistar rats were divided into seven cohorts and given daily injections (i.p.) of AMI (5mg/kg) or saline throughout the duration of the study. In parallel, various cohorts of intact or parkinsonian animals were sacrificed at specific time points to determine the impact of AMI treatment on trophic factor levels in the intact and degenerating nigrostriatal system. The left and right hemispheres of the substantia nigra, striatum, frontal cortex, piriform cortex, hippocampus and anterior cingulate cortex were dissected and BDNF and GDNF levels were measured with ELISA. Results show that chronic AMI treatment elicits effects in multiple brain regions and differentially regulates levels of BDNF and GDNF depending on the region. Additionally, AMI halts the progressive degeneration of dopamine (DA) neurons elicited by an intrastriatal 6-OHDA lesion. Taken together, these results suggest that AMI treatment elicits significant trophic changes important to DA neuron survival within both the intact and degenerating nigrostriatal system.
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影响因子：
2
作者：
Gundersen, HJG;Jensen, EBV;Nielsen, J
通讯作者：
Nielsen, J
影响因子：
5.3
作者：
Åkerud, P;Canals, JM;Arenas, E
通讯作者：
Arenas, E
影响因子：
4.7
作者：
Coppell, AL;Pei, Q;Zetterström, TSC
通讯作者：
Zetterström, TSC
影响因子：
82.9
作者：
Gill, SS;Patel, NK;Heywood, P
通讯作者：
Heywood, P
DOI：
10.1016/0306-3623(95)02008-x
发表时间：
1996-03-01
期刊：
GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM
影响因子：
--
作者：
Coudore, F;Besson, A;Fialip, J
通讯作者：
Fialip, J