Intestinal Permeability, Dysbiosis, Inflammation and Enteric Glia Cells: The Intestinal Etiology of Parkinson’s Disease

Yang, Hualin; Li, Song; Le, Weidong

doi:10.14336/ad.2022.01281

Cited by 18 publications

(13 citation statements)

References 85 publications

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“…However, the hypothesis that the enteric glia is affected by ZIKV infection in vivo, as well as the possible consequences of this infection, have yet to be demonstrated. Of note, accumulating evidence has revealed that GI disorders are possible pathological initiators of PD many years before it progresses to the CNS, with an important role for enteric glial cells (Yang et al, 2022).…”

Section: Glial Cells As Targets Of Zikv Infectionmentioning

confidence: 99%

The role of glial cells in Zika virus‐induced neurodegeneration

Quincozes‐Santos

Bobermin

Costa

et al. 2023

Glia

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Zika virus (ZIKV) is a strongly neurotropic flavivirus whose infection has been associated with microcephaly in neonates. However, clinical and experimental evidence indicate that ZIKV also affects the adult nervous system. In this regard, in vitro and in vivo studies have shown the ability of ZIKV to infect glial cells. In the central nervous system (CNS), glial cells are represented by astrocytes, microglia, and oligodendrocytes. In contrast, the peripheral nervous system (PNS) constitutes a highly heterogeneous group of cells (Schwann cells, satellite glial cells, and enteric glial cells) spread through the body. These cells are critical in both physiological and pathological conditions; as such, ZIKV-induced glial dysfunctions can be associated with the development and progression of neurological complications, including those related to the adult and aging brain. This review will address the effects of ZIKV infection on CNS and PNS glial cells, focusing on cellular and molecular mechanisms, including changes in the inflammatory response, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate homeostasis, neural metabolism, and neuron-glia communication. Of note, preventive and therapeutic strategies that focus on glial cells may emerge to delay and/or prevent the development of ZIKV-induced neurodegeneration and its consequences.André Quincozes-Santos and Larissa Daniele Bobermin contributed equally to this work.

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Section: Glial Cells As Targets Of Zikv Infectionmentioning

confidence: 99%

The role of glial cells in Zika virus‐induced neurodegeneration

Quincozes‐Santos

Bobermin

Costa

et al. 2023

Glia

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“…Recent studies have provided evidence that PD results from an alteration in the gut microbiota, characterized by changes in gut permeability due to an increase in pathogenic bacteria [ 31 ]. Compared to the Saline + Vehicle group, the MPTP + Vehicle group showed increased expression of the proinflammatory cytokines IL-12a in mice, although it showed no significant difference in expression.…”

Section: Resultsmentioning

confidence: 99%

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

Qiao,

Huang,

Zhou

et al. 2024

Brain Sciences

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Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

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“…Gastrointestinal disorders and inflammation commonly occur in PD patients [ 44 ]. To demonstrate the effect of FMT from PD patients and healthy human controls on the colon in MPTP-treated mice, we tested inflammation in the gut via H&E staining, immunofluorescence and western blotting.…”

Section: Resultsmentioning

confidence: 99%

Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway

et al. 2023

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Increasing evidence has shown that gut dysbacteriosis may play a crucial role in neuroinflammation in Parkinson's disease (PD). However, the specific mechanisms that link gut microbiota to PD remain unexplored. Given the critical roles of blood-brain barrier (BBB) dysfunction and mitochondrial dysfunction in the development of PD, we aimed to evaluate the interactions among the gut microbiota, BBB, and mitochondrial resistance to oxidation and inflammation in PD. We investigated the effects of fecal microbiota transplantation (FMT) on the physiopathology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. The aim was to explore the role of fecal microbiota from PD patients and healthy human controls in neuroinflammation, BBB components, and mitochondrial antioxidative capacity via the AMPK/SOD2 pathway. Compared to control mice, MPTP-treated mice exhibited elevated levels of Desulfovibrio, whereas mice given FMT from PD patients exhibited enriched levels of Akkermansia and mice given FMT from healthy humans showed no significant alterations in gut microbiota. Strikingly, FMT from PD patients to MPTP-treated mice significantly aggravated motor impairments, dopaminergic neurodegeneration, nigrostriatal glial activation and colonic inflammation, and inhibited the AMPK/SOD2 signaling pathway. However, FMT from healthy human controls greatly improved the aforementioned MPTP-caused effects. Surprisingly, the MPTP-treated mice displayed a significant loss in nigrostriatal pericytes, which was restored by FMT from healthy human controls. Our findings demonstrate that FMT from healthy human controls can correct gut dysbacteriosis and ameliorate neurodegeneration in the MPTP-induced PD mouse model by suppressing microgliosis and astrogliosis, ameliorating mitochondrial impairments via the AMPK/SOD2 pathway, and restoring the loss of nigrostriatal pericytes and BBB integrity. These findings raise the possibility that the alteration in the human gut microbiota may be a risk factor for PD and provide evidence for potential application of FMT in PD preclinical treatment.

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Intestinal Permeability, Dysbiosis, Inflammation and Enteric Glia Cells: The Intestinal Etiology of Parkinson’s Disease

Cited by 18 publications

References 85 publications

The role of glial cells in Zika virus‐induced neurodegeneration

The role of glial cells in Zika virus‐induced neurodegeneration

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway

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