Kim Ji Eun, Kwon Ki Chun, Jin You Jeong, Seol Ayun, Song Hee Jin, Roh Yu Jeong, Kim Tae Ryeol, Park Eun Seo, Park Gi Ho, Park Ji Won, Jung Young Suk, Cho Joon Yong, Hwang Dae Youn
Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute/Laboratory Animal Resources Center, Pusan National University, Miryang, Korea.
Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, South Korea.
Lab Anim Res. 2023 Nov 15;39(1):30. doi: 10.1186/s42826-023-00181-4.
The gut-brain axis (GBA) in Parkinson's disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model.
The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSE-hαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity.
The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.
尽管肠道微生物群失调被认为是神经退行性疾病的主要治疗靶点之一，但帕金森病（PD）中的肠-脑轴（GBA）仅在有限的小鼠模型中进行了研究。因此，本研究检测了在神经元特异性烯醇化酶（NSE）调控下过表达人α-突触核蛋白（hαSyn）的新型转基因（Tg）小鼠粪便微生物群的组成变化，以分析其作为GBA模型的潜力。
NSE-hαSyn Tg小鼠黑质和纹状体中αSyn蛋白的表达水平显著高于非Tg小鼠，而同一组中酪氨酸羟化酶（TH）的表达水平降低。此外，在NSE-hαSyn Tg小鼠中检测到跌倒次数减少了72.7%，跌倒次数增加了3.8倍。NSE-hαSyn Tg小鼠胃肠道（GI）组织学结构的绒毛厚度和隐窝长度减小。此外，在微生物群丰富度和多样性增加期间，NSE-hαSyn Tg小鼠的11个属显著增加，包括粪杆菌属、梭菌属、费氏杆菌属、毛螺菌属和乙酸杆菌属，而仅两个属的利氏乳杆菌属和桑氏杆菌属减少。
NSE-hαSyn Tg小鼠的运动协调和平衡功能障碍可能与肠道微生物群的组成变化有关。此外，这些小鼠具有作为GBA模型的潜力。
