Protective effects of prucalopride in MPTP-induced Parkinson’s disease mice: Neurochemistry, motor function and gut barrier

Shi, Yun; Qiao, Chen-Meng; Zhou, Yu; Wu, Ji Yuan; Cui, Chun; Hong, Hui; Jia, Xiaoyun; Huang, Saisai; Yao, Li; Zhao, Wenjin; Shen, Yan‐Qin

doi:10.1016/j.bbrc.2021.03.109

Cited by 6 publications

(6 citation statements)

References 33 publications

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“…IF, WB, and HPLC showed that TMAO had no significant effect on the loss of dopamine neurons, TH expression, or DA content reduction in the SN and striatum of the PD mice. Previous studies in our laboratory have shown an increase in the striatum DA metabolic rate in MPTP-induced PD mice [24,25]. In this study, compared with the MPTP group, the DOPAC content, HVA/DA ratio, and DOPAC/DA ratio (DA metabolic rate index) were significantly increased in the TMAO + MPTP group, indicating that TMAO exacerbated DA metabolism in the PD mice.…”

Section: Discussionsupporting

confidence: 53%

Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease

et al. 2023

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Observational studies have shown abnormal changes in trimethylamine N-oxide (TMAO) levels in the peripheral circulatory system of Parkinson’s disease (PD) patients. TMAO is a gut microbiota metabolite that can cross the blood–brain barrier and is strongly related to neuroinflammation. Neuroinflammation is one of the pathological drivers of PD. Herein, we investigated the effect of TMAO on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. TMAO pretreatment was given by adding 1.5% (w/v) TMAO to the drinking water of the mice for 21 days; then, the mice were administered MPTP (20 mg/kg, i.p.) four times a day to construct an acute PD model. Their serum TMAO concentrations, motor function, dopaminergic network integrity, and neuroinflammation were then assayed. The results showed that TMAO partly aggravated the motor dysfunction of the PD mice. Although TMAO had no effect on the dopaminergic neurons, TH protein content, and striatal DA level in the PD mice, it significantly reduced the striatal 5-HT levels and aggravated the metabolism of DA and 5-HT. Meanwhile, TMAO significantly activated glial cells in the striatum and the hippocampi of the PD mice and promoted the release of inflammatory cytokines in the hippocampus. In summary, higher-circulating TMAO had adverse effects on the motor capacity, striatum neurotransmitters, and striatal and hippocampal neuroinflammation in PD mice.

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Section: Discussionsupporting

confidence: 53%

Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease

et al. 2023

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“…One study showed that the administration of 5-HT 4 receptor agonists did not improve motor impairment [83]. On the contrary, a 7-day administration of prucalopride, a 5-HT 4 agonist, induced a beneficial effect on motor deficits (bradykinesia, exploration, balance, and muscle strength) in the parkinsonian mice, by attenuating the striatal loss of dopamine [89]. Studies that have simply analyzed variations in receptor expression without using pharmacological ligands show divergent results.…”

Section: Movement Disordersmentioning

confidence: 99%

“…Patients affected by Parkinson's disease Motor functions improved [94] Mouse model of Parkinson's disease No motor improvement [83] Motor deficits improved associated with rescued striatal dopamine levels [89] 5-HT4 receptor antagonist…”

Section: -Ht4 Receptor Agonistmentioning

confidence: 99%

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The Serotonin 4 Receptor Subtype: A Target of Particular Interest, Especially for Brain Disorders

Sgambato

2024

IJMS

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In recent years, particular attention has been paid to the serotonin 4 receptor, which is well expressed in the brain, but also peripherally in various organs. The cerebral distribution of this receptor is well conserved across species, with high densities in the basal ganglia, where they are expressed by GABAergic neurons. The 5-HT4 receptor is also present in the cerebral cortex, hippocampus, and amygdala, where they are carried by glutamatergic or cholinergic neurons. Outside the central nervous system, the 5-HT4 receptor is notably expressed in the gastrointestinal tract. The wide distribution of the 5-HT4 receptor undoubtedly contributes to its involvement in a plethora of functions. In addition, the modulation of this receptor influences the release of serotonin, but also the release of other neurotransmitters such as acetylcholine and dopamine. This is a considerable asset, as the modulation of the 5-HT4 receptor can therefore play a direct or indirect beneficial role in various disorders. One of the main advantages of this receptor is that it mediates a much faster antidepressant and anxiolytic action than classical selective serotonin reuptake inhibitors. Another major benefit of the 5-HT4 receptor is that its activation enhances cognitive performance, probably via the release of acetylcholine. The expression of the 5-HT4 receptor is also altered in various eating disorders, and its activation by the 5-HT4 agonist negatively regulates food intake. Additionally, although the cerebral expression of this receptor is modified in certain movement-related disorders, it is still yet to be determined whether this receptor plays a key role in their pathophysiology. Finally, there is no longer any need to demonstrate the value of 5-HT4 receptor agonists in the pharmacological management of gastrointestinal disorders.

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“…In contrast, Nec-1-treated PD mice (Nec-1 + MPTP) spent significantly less time climbing the pole, suggesting that Nec-1 treatment could efficiently ameliorate the motor deficit in MPTP induced PD model (Figure 3A). Open field tests were utilized to investigate and gauge the anxiety and curiosity of mice [17]. As shown in Figure 3B-E, the grid number, average speed and total distance of PD mice were reduced greatly compared to control mice.…”

Section: Inhibition Of Ripk1 Improves Mptp Induced Motor and Non-moto...mentioning

confidence: 99%

RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease

et al. 2023

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Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated in the brain in PD mouse models. Here, we aim to explore the role of RIPK1 in regulating the neuroinflammation of PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg four times/day), followed by necrostatin-1 treatment (Nec-1, RIPK1 inhibitor; 1.65 mg/kg once daily for seven days. Notably, the first Nec-1 was given 12 h before MPTP modeling). Behavioral tests indicated that inhibition of RIPK1 greatly relieved motor dysfunction and anxiety-like behaviors of PD mice. It also increased striatal TH expression, rescue the loss of dopaminergic neurons, and reduce activation of astrocytes in the striatum of PD mice. Furthermore, inhibition of RIPK1 expression reduced A1 astrocytes’ relative gene expression (CFB, H2-T23) and inflammatory cytokine or chemokine production (CCL2, TNF-α, IL-1β) in the striatum of PD mice. Collectively, inhibition of RIPK1 expression can provide neuroprotection to PD mice, probably through inhibition of the astrocyte A1 phenotype, and thus RIPK1 might be an important target in PD treatment.

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Protective effects of prucalopride in MPTP-induced Parkinson’s disease mice: Neurochemistry, motor function and gut barrier

Cited by 6 publications

References 33 publications

Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease

Trimethylamine N-Oxide Exacerbates Neuroinflammation and Motor Dysfunction in an Acute MPTP Mice Model of Parkinson’s Disease

The Serotonin 4 Receptor Subtype: A Target of Particular Interest, Especially for Brain Disorders

RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease

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