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药物诱导的帕金森病调节小鼠嗅球中的蛋白激酶A和嗅觉标记蛋白。

Drug-induced Parkinson's disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb.

作者信息

Mucignat Carla, Caretta Antonio

机构信息

Department of Molecular Medicine, University of Padova, Via Marzolo, 3, 35131, Padua, Italy.

INBB, National Insitute of Biostructures and Biosystems, Rome, Italy.

出版信息

Behav Brain Funct. 2017 Jan 26;13(1):1. doi: 10.1186/s12993-017-0119-2.

Abstract

BACKGROUND

Olfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice.

FINDINGS

Lesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission. MPTP induced motor impairment, but no deficit in olfactory search. Thyrosine hydroxylase did not differ in olfactory bulb, while a strong decrease was detected in substantia nigra and tegmentum of MPTP mice. Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in the inner granular layer of MPTP mice.

CONCLUSIONS

MPTP mice do not present behavioural deficits in olfactory search, yet immunoreactivity reveals modifications in the olfactory bulb, and suggests changes in intracellular signal processing, possibly linked to neuron survival after MPTP.

摘要

背景

嗅觉在帕金森病患者中常常受到影响,但嗅球中的多巴胺能细胞不受某些诱发帕金森病的药物影响。我们研究了药物MPTP是否会导致帕金森病典型的嗅觉缺陷,并影响小鼠的嗅球。

研究结果

对损伤小鼠和对照小鼠进行嗅觉搜索、运动和探索行为测试。通过免疫组织化学研究大脑和嗅觉黏膜中的酪氨酸羟化酶、嗅觉标记蛋白和环磷酸腺苷依赖性蛋白激酶,其作为多巴胺能神经传递所涉及的细胞内途径。MPTP诱导运动障碍,但嗅觉搜索无缺陷。酪氨酸羟化酶在嗅球中无差异,而在MPTP小鼠的黑质和被盖中检测到显著下降。嗅觉标记蛋白在MPTP小鼠的嗅球中减少,而环磷酸腺苷依赖性蛋白激酶在MPTP小鼠的内颗粒层中增加。

结论

MPTP小鼠在嗅觉搜索中没有行为缺陷,但免疫反应性显示嗅球有改变,并提示细胞内信号处理发生变化,这可能与MPTP后的神经元存活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c263/5267367/5d4ac8ffdbb7/12993_2017_119_Fig1_HTML.jpg

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