Effect of Coffee against MPTP-Induced Motor Deficits and Neurodegeneration in Mice Via Regulating Gut Microbiota

Abstract

The mechanisms of coffee against Parkinson disease (PD) remained incompletely elucidated. Numerous studies suggested that gut microbiota played a crucial role in the pathogenesis of PD. Here, we explored the further mechanisms of coffee against PD via regulating gut microbiota. C57BL/6 mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce a PD mouse model, then treated with coffee for 4 consecutive weeks. Behavioral tests consisting of the pole test and beam-walking test were conducted to evaluate the motor function of mice. The levels of tyrosine hydroxylase (TH) and α-synuclein (α-syn) were assessed for dopaminergic neuronal loss. The levels of occludin, glial fibrillary acidic protein (GFAP), Bcl-2, Bax, cleaved caspase-3, and cytochrome c (Cyt c) were detected. Moreover, microbial components were measured by 16s rRNA sequencing. Our results showed that coffee significantly improved the motor deficits and TH neuron loss, and reduced the level of α-syn in the MPTP-induced mice. Moreover, coffee increased the level of BBB tight junction protein occludin and reduced the level of astrocyte activation marker GFAP in the MPTP-induced mice. Furthermore, coffee significantly decreased the levels of proapoptotic proteins, including Bax, cleaved caspase-3, and cytochrome c, while it increased the level of antiapoptotic protein Bcl-2, consequently preventing MPTP-induced apoptotic cascade. Moreover, coffee improved MPTP-induced gut microbiota dysbiosis. These findings suggested that the neuroprotective effects of coffee on PD were involved in the regulation of gut microbiota, which might provide a novel option to elucidate the effects of coffee on PD.

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

“…Furthermore, previous studies have reported that coffee contains possible neuroprotective compounds such as caffeine and neuroprotective polyphenols (122,123). Coffee can ameliorate motor deficits and dopaminergic neuronal loss, and reduce a-synuclein aggregation in MPTP-induced mice via regulating gut microbiota (124). Coffee can increase the level of anti-inflammatory Bifidobacteria and decrease the levels of Clostridium spp.…”

Carnosol Reduced Pathogenic Protein Aggregation and Cognitive Impairment in Neurodegenerative Diseases Models via Improving Proteostasis and Ameliorating Mitochondrial Disorders

“…It also suggested that CL might alleviate cognitive impairment in the PD model by improving DA neuron damage. However, the main culprit behind the death of DA neurons in PD patients is the abnormal accumulation of α-syn. , To better understand the role of CL-intervention in the deposition of α-syn, another strain NL5901, expressing age-related α-syn together with GFP in vivo, was used to detect α-syn accumulation. As shown in Figure F, CL reduced the number of α-syn aggregates in NL5901.…”

Gastrodia elata polysaccharide alleviates Parkinson's disease via inhibiting apoptotic and inflammatory signaling pathways and modulating the gut microbiota

“…Motor dysfunction was confirmed using rotarod and pole tests in MPTP-induced PD mice, consistent with previous reports. [65][66][67] The loss of DA neurons leads to reduced dopamine, which is responsible for motor dysfunction in PD patients. 68 TH, a marker of DA neurons, is an enzyme necessary for the synthesis of dopamine.…”

“…[4][5][6] Under the stimulation of α-SYN accumulation and neurotoxins such as MPTP, mitochondrial apoptosis is triggered, leading to the loss of DA neurons. 7 Therefore, apoptosis is one of the important pathogenesis factors of PD. Moreover, neuroinflammation is another contributor that causes or aggravates PD.…”