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利血平诱导的帕金森病进展模型中的遗传效应

Genetic effects in a progressive model of parkinsonism induced by reserpine.

作者信息

Fadanni Guilherme Pasetto, Leão Anderson Henrique França Figueiredo, Granzotto Natalli, Pereira Aline Guimarães, de Gois Auderlan Mendonça, Anjos Pâmela Andressa Ramborger, Linder Áurea Elizabeth, Santos José Ronaldo, Silva Regina Helena, Izídio Geison Souza

机构信息

Graduate Program of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.

Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.

出版信息

Psychopharmacology (Berl). 2023 May;240(5):1131-1142. doi: 10.1007/s00213-023-06350-6. Epub 2023 Mar 24.

Abstract

OBJECTIVE AND METHODS

We investigated the locomotor, emotional, physiological, and neurobiological effects induced by low-dose reserpine repeated treatment (0.1 mg/kg; 14 injections) in males from the Lewis (LEW), Spontaneously Hypertensive Rats (SHR), and SHR.LEW-(D4Rat76-D4Mgh11) (SLA16) isogenic rat strains, which have different genetic backgrounds on chromosome 4. Behavioral responses in the catalepsy, open-field, and oral movements' tests were coupled with blood pressure, body weight, and striatal tyrosine hydroxylase (TH) level assessments to establish neurobiological comparisons between reserpine-induced impairments and genetic backgrounds RESULTS: Results revealed the SHR strain was more sensitive in the catalepsy test and exhibited higher TH immunoreactivity in the dorsal striatum. The SLA16 strain presented more oral movements, suggesting increased susceptibility to develop oral dyskinesia.

CONCLUSIONS

Our results showed the efficacy of repeated treatment with a low dose of reserpine and demonstrated, for the first time, the genetic influence of a specific region of chromosome 4 on the expression of these effects.

摘要

目的与方法

我们研究了低剂量利血平重复治疗(0.1毫克/千克;14次注射)对来自Lewis(LEW)、自发性高血压大鼠(SHR)以及SHR.LEW-(D4Rat76-D4Mgh11)(SLA16)同基因大鼠品系雄性大鼠的运动、情绪、生理和神经生物学影响,这些品系在4号染色体上具有不同的遗传背景。在僵住症、旷场试验和口腔运动测试中的行为反应与血压、体重及纹状体酪氨酸羟化酶(TH)水平评估相结合,以建立利血平诱导损伤与遗传背景之间的神经生物学比较。结果:结果显示SHR品系在僵住症测试中更敏感,且在背侧纹状体中表现出更高水平的TH免疫反应性。SLA16品系出现更多的口腔运动,表明其发生口腔运动障碍的易感性增加。

结论

我们的结果显示了低剂量利血平重复治疗的效果,并首次证明了4号染色体特定区域对这些效应表达的遗传影响。

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