多巴胺D2受体激活在实验帕金森症中抵消嗅觉功能障碍和相关的细胞异常
Daniel Medeiros1, Débora Masini1, Carina Plewnia1
1Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Heliyon
|September 3, 2024
概括
普拉米佩克索尔是一种多巴胺激动剂,在帕金森病 (PD) 的小鼠模型中改善了嗅觉功能障碍. 这种治疗使嗅球中的多巴胺水平和脑波活动正常化,这表明了PD相关的嗅觉丧失的潜在治疗机制.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 帕金森病研究 帕金森病研究
背景情况:
- 嗅觉功能障碍是帕金森病 (PD) 的一个常见的,早期的非运动性症状,通常在运动缺陷之前.
- 与PD相关的嗅觉功能障碍的潜在机制尚不清楚.
- 使用6-氧多巴胺 (6-OHDA) 病变的小鼠模型被开发用于研究早期PD嗅觉缺陷.
研究的目的:
- 在早期PD小鼠模型中调查多巴胺D2/3激动剂pramipexole对嗅觉功能障碍的治疗潜力.
- 探索普拉米醇对与PD相关的嗅球 (OB) 中细胞和电生理异常的影响.
主要方法:
- 通过部分6-氧多巴胺 (6-OHDA) 损伤背上条纹体,生成了早期帕金森病的小鼠模型.
- 在PD小鼠模型中长期和连续使用pramipexole.
- 使用习惯性/失习性测试来评估嗅觉歧视.
- 在嗅球 (OB) 中分析了多巴胺细胞计数和铁酸酶水平.
- 在OB中记录局部场电位 (LFP),以评估β频振荡.
主要成果:
- 普拉米醇治疗成功地恢复了6-OHDA受损小鼠的受损嗅觉歧视.
- 该药物消除了PD模型小鼠的嗅球 (OB) 中多巴胺细胞和氨酸氧酶水平的增加.
- 普拉米醇使受损小鼠的嗅球 (OB) 中降低的β频率振荡正常化,这表明恢复了远程OB传输.
结论:
- 在帕金森症的实验模型中,长时间服用普拉米佩克索尔有效地挽救了嗅觉歧视缺陷.
- 普拉米醇的保护作用与多巴胺神经元活动和OBβ频段振荡的正常化有关.
- 这些发现为帕金森病的嗅觉功能障碍背后的机制提供了洞察力,并突出了普拉米醇的潜在治疗作用.
相关概念视频
01:24Parkinson's Disease: Treatment
239
Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
239
01:15Parkinson's Disease: Overview
499
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
499
01:29Drugs Affecting Neurotransmitter Synthesis
1.3K
Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
1.3K
01:28Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists
281
Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
281
01:37Neural Regulation
39.2K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.2K