帕金森病大鼠模型中呼吸状态依赖性改变

Jean Jacques Walker, Estelle Meunier, Samuel Garcia, Belkacem Messaoudi, Anne-Marie Mouly, Alexandra Veyrac, Nathalie Buonviso, Emmanuelle Courtiol
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摘要

帕金森病(PD)是第二常见的神经退行性疾病。除了运动协调方面的重大缺陷外,患者还可能表现出感觉和认知障碍,尽管这是PD症状学的固有部分,但往往被忽视。在这些症状中,参与调节多种生理和神经元过程的关键机制呼吸似乎发生了改变。重要的是,呼吸模式与动物的行为状态高度相关,尽管已经在不同的PD模型中研究了呼吸,但尚未有研究考虑到这些模型中行为状态对呼吸缺陷的潜在影响。为了探索这一变量,我们首先表征了神经毒素诱导的PD (6-OHDA)大鼠模型在不同警戒状态(睡眠、安静清醒和探索)下的呼吸参数。我们注意到6-OHDA大鼠在安静清醒时的呼吸频率明显高于Sham大鼠。6-OHDA大鼠在安静清醒和探索时均有较高的呼吸振幅。在睡眠期间没有观察到治疗的效果。考虑到呼吸和嗅觉之间的关系以及PD患者嗅觉缺陷的存在,我们随后使用气味习惯/交叉习惯范式研究了PD大鼠的气味诱发嗅探反应。通过嗅探频率评估,两组之间的嗅觉能力没有明显差异。这些结果证实了6-OHDA大鼠的呼吸损伤是警惕性依赖的假设。我们的研究结果还揭示了在分析呼吸时将行为状态作为影响因素考虑的重要性。
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State-dependent alteration of respiration in a rat model of Parkinson disease
Parkinson disease (PD) is the second most frequent neurodegenerative disorder. Besides major deficits in motor coordination, patients may also display sensory and cognitive impairments, which are often overlooked despite being inherently part of the PD symptomatology. Amongst those symptoms, respiration, a key mechanism involved in the regulation of multiple physiological and neuronal processes, appears to be altered. Importantly, breathing patterns are highly correlated with the animal's behavioral states, and although respiration has been investigated in different models of PD, no study has yet taken into consideration the potential impact of behavioral state on respiration deficits in these models. To explore this variable, we first characterized the respiratory parameters in a neurotoxin-induced rat model of PD (6-OHDA) across different vigilance states: sleep, quiet waking and exploration. We noted a significantly higher respiratory frequency in 6-OHDA rats during quiet waking compared to Sham rats. A higher respiratory amplitude was also observed in 6-OHDA rats during both quiet waking and exploration. No effect of the treatment was noted during sleep. Given the relation between respiration and olfaction and the presence of olfactory deficits in PD patients, we then investigated the odor-evoked sniffing response in PD rats, using an odor habituation/cross-habituation paradigm. No substantial differences were observed in olfactory abilities between the two groups, as assessed through sniffing frequency. These results corroborate the hypothesis that respiratory impairments in 6-OHDA rats are vigilance-dependent. Our results also shed light on the importance of considering the behavioral state as an impacting factor when analyzing respiration.
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