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MPTP 处理的普通狨猴纹状体和纹状体外多巴胺摄取位点的短期和长期变化。

Short- and long-term changes in striatal and extrastriatal dopamine uptake sites in the MPTP-treated common marmoset.

作者信息

Gnanalingham K K, Milkowski N A, Smith L A, Hunter A J, Jenner P, Marsden C D

机构信息

Parkinson's Disease Society Experimental Research Laboratories, King's College, London, UK.

出版信息

Eur J Pharmacol. 1995 Apr 24;277(2-3):235-41. doi: 10.1016/0014-2999(95)00086-z.

Abstract

The 'short-term' (15-30 days) and 'long-term' (18-42 months) effects of the systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on [3H]mazindol binding to dopamine uptake sites was investigated in the common marmoset. In the 'short-term' MPTP-treated group, [3H]mazindol binding was reduced in the caudate-putamen (by -82 to -98% with respect to controls), substantia nigra pars compacta (-71 to -84%), ventral tegmental area (-72%) and nucleus accumbens (-54%). [3H]Mazindol binding in the globus pallidus, frontal cortex and substantia nigra pars reticulata was much lower and was unaffected by MPTP treatment. In the 'long-term' MPTP-treated group [3H]mazindol binding was still greatly reduced in the substantia nigra pars compacta (by -76 to -89%), ventral tegmental area (-71%) and most of the caudate-putamen (-69 to -98%), although the reduction in [3H]mazindol binding in the nucleus accumbens (-27%) and rostroventral caudate nucleus (-69%) was less than in the 'short-term' MPTP-treated group. The motor deficits induced by MPTP treatment in the common marmoset are largely reversible with increasing survival times (Ueki et al., 1989, Neuropharmacology 28, 1089). In the present study, the apparent 'recovery' in [3H]mazindol binding in the rostroventral caudate nucleus and nucleus accumbens may indicate regeneration of dopamine neurone terminals in these regions and this may contribute to the behavioural recovery seen in this primate model of Parkinson's disease.

摘要

研究了在普通狨猴中,全身给予1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)对[³H]马吲哚与多巴胺摄取位点结合的“短期”(15 - 30天)和“长期”(18 - 42个月)影响。在“短期”MPTP处理组中,[³H]马吲哚结合在尾状核 - 壳核(相对于对照组减少 - 82%至 - 98%)、黑质致密部(- 71%至 - 84%)、腹侧被盖区(- 72%)和伏隔核(- 54%)减少。苍白球、额叶皮质和黑质网状部的[³H]马吲哚结合低得多,且不受MPTP处理影响。在“长期”MPTP处理组中,黑质致密部(- 76%至 - 89%)、腹侧被盖区(- 71%)和大部分尾状核 - 壳核(- 69%至 - 98%)的[³H]马吲哚结合仍大幅减少,尽管伏隔核(- 27%)和吻腹侧尾状核(- 69%)的[³H]马吲哚结合减少程度小于“短期”MPTP处理组。MPTP处理在普通狨猴中诱导的运动缺陷随着存活时间增加在很大程度上是可逆的(Ueki等人,1989年,《神经药理学》28卷,1089页)。在本研究中,吻腹侧尾状核和伏隔核中[³H]马吲哚结合的明显“恢复”可能表明这些区域多巴胺神经元终末的再生,这可能有助于在这个帕金森病灵长类模型中观察到的行为恢复。

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