Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: Comparison of intraventricular and intranigral delivery
Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: Comparison of intraventricular and intranigral delivery
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DOI：
10.1016/s0306-4522(97)83045-x
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发表时间：
1997-05-01
期刊：
影响因子：
3.3
通讯作者：
Jiao, S
中科院分区：
文献类型：
--
作者：
Lapchak, PA;Miller, PJ;Jiao, S
黑质内或脑室内给药的胶质细胞源性神经营养因子的影响进行了测试低剂量（0.05毫克/公斤）阿朴吗啡诱导的关系和酪氨酸羟化酶活性在黑质和纹状体的稳定6-羟基多巴胺损伤大鼠。此外，我们确定了6-羟基多巴胺病变的存在或不存在的治疗影响神经肽（P物质，甲硫氨酸脑啡肽，强啡肽）含量在纹状体。胶质细胞源性神经营养因子，当给予intrinigrally，防止阿扑吗啡诱导的旋转行为11周后，一次注射。相比之下，脑室注射胶质细胞源性神经营养因子产生了短暂的旋转行为减少，持续两到三个星期后，单次注射。我们还表明，旋转行为减少后，每次随后的脑室内注射胶质细胞源性神经营养因子给予每六周，一个时间点时，基线旋转赤字重新建立。在这项研究中，在所有6-羟基多巴胺损伤的大鼠中，神经胶质细胞系源性神经营养因子的脑内或脑室内给药显著降低了体重增加。行为分析后，确认改善的行为被建立，组织进行了解剖neurochemical analysis.In intrinigral注射给药的胶质细胞系衍生的神经营养因子的损伤大鼠，黑质，但不是纹状体酪氨酸羟化酶活性的显着增加进行了测量。此外，6-羟基多巴胺损伤显著增加纹状体强啡肽（61-139%）和甲硫氨酸脑啡肽（81-139%），但P物质水平没有增加。在这些大鼠中，神经胶质细胞源性神经营养因子注射逆转病变引起的黑质强啡肽A水平升高和黑质多巴胺水平升高，但不改变黑质甲硫氨酸脑啡肽或P物质水平，也不改变纹状体多巴胺水平。在脑室内注射胶质细胞源性神经营养因子的损伤大鼠中，病变同侧的黑质酪氨酸羟化酶增加，但不在纹状体。脑室内给药胶质细胞系衍生的神经营养因子不能逆转黑质强啡肽A或甲硫氨酸脑啡肽水平的损伤诱导的增加，胶质细胞系衍生的神经营养因子也不能影响纹状体中的P物质水平。这些结果表明，在帕金森病的动物模型中，神经营养因子胶质细胞系衍生的神经营养因子逆转了6-羟基多巴胺给药的行为后果，一种可能涉及多巴胺能和肽能神经传递的作用。(C)1997年IBRO。
The effects of intranigrally- or intraventricularly-administered glial cell line-derived neurotrophic factor were tested on low dose (0.05 mg/kg) apomorphine-induced relations and tyrosine hydroxylase activity in the substantia nigra and striatum of stable 6-hydroxydopamine-lesioned rats. In addition, we determined if 6-hydroxydopamine lesions in the absence or presence of treatment affected neuropeptide (substance P, met-enkephalin, dynorphin) content in the striatum. Glial cell line-derived neurotrophic factor, when administered intranigrally, prevented apomorphine-induced rotational behaviour for 11 weeks following a single injection. In comparison, intraventricularly-administered glial cell line-derived neurotrophic factor produced a transient reduction in rotational behaviour that lasted for two to three weeks following a single injection. We also show that rotational behaviour is reduced following each subsequent intraventricular injection of glial cell line-derived neurotrophic Factor given every six weeks, a time-point when baseline rotation deficits were re-established. Intranigrally- or intraventricularly administered glial cell line-derived neurotrophic factor significantly reduced weight gain in all 6-hydroxydopamine-lesioned rats in this study. Following behavioural analysis where a confirmed improvement of behaviour was established, tissues were dissected for neurochemical analysis.In lesioned rats with intranigral injections of administered glial cell line-derived neurotrophic factor, significant increases of nigral, but not striatal tyrosine hydroxylase activity were measured. Additionally, 6-hydroxydopamine lesions significantly increased striatal dynorphin (61-139%) and met-enkephalin (81-139%), but not substance P levels. In these rats, intranigrally-administered glial cell line-derived neurotrophic factor injections reversed lesion-induced increases in nigral dynorphin A levels and increased nigral dopamine levels, but did not alter nigral met-enkephalin or substance P levels nor striatal dopamine levels. In lesioned rats with intraventricular injections of glial cell line-derived neurotrophic factor, tyrosine hydroxylase ispilateral to the lesion was increased in the substantia nigra, but not in the striatum. Intraventricularly-administered glial cell line-derived neurotrophic factor did not reverse lesion-induced increases in nigral dynorphin A or met-enkephalin levels nor did glial cell line-derived neurotrophic factor affect substance P levels in the striatum.These results suggest that in an animal model of Parkinson's disease, the neurotrophic Factor glial cell line-derived neurotrophic Factor reverses behavioural consequences of 6-hydroxydopamine administration, an effect that may involve both dopaminergic and peptidergic neurotransmission. (C) 1997 IBRO.