bims-metalz 2023-10-15 papers

bims-metalz

Biomed News

on Metabolic causes of Alzheimer’s disease

Issue of 2023–10–15
seven papers selected by
Mikaila Chetty, Goa University

Impact of Microbiome-Brain Communication on Neuroinflammation and Neurodegeneration.
Cadmium alters whole animal ionome and promotes the re-distribution of iron in intestinal cells of Caenorhabditis elegans.
Role of Bmal1 and Gut Microbiota in Alzheimer's Disease and Parkinson's Disease Pathophysiology: The Probable Effect of Melatonin on Their Association.
Cell-Type-Specific Mitochondrial Quality Control in the Brain: A Plausible Mechanism of Neurodegeneration.
Effects of Vitamin E on the Gut Microbiome in Ageing and Its Relationship with Age-Related Diseases: A Review of the Current Literature.
The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications.
Exposure to epoxy-modified nanoplastics in the range of μg/L causes dysregulated intestinal permeability, reproductive capacity, and mitochondrial homeostasis by affecting antioxidant system in Caenorhabditis elegans.

Int J Mol Sci. 2023 Oct 05. pii: 14925. [Epub ahead of print]24(19):

Impact of Microbiome-Brain Communication on Neuroinflammation and Neurodegeneration.

Iris Stolzer, Eveline Scherer, Patrick Süß, Veit Rothhammer, Beate Winner, Markus F Neurath, Claudia Günther.

  The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations in microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both the digestive tract and the central nervous system (CNS). This complex interplay between the microbiota, the gut, and the CNS is referred to as the gut-brain axis. The role of the gut microbiota in the pathogenesis of neurodegenerative diseases has gained increasing attention in recent years, and evidence suggests that gut dysbiosis may contribute to disease development and progression. Clinical studies have shown alterations in the composition of the gut microbiota in multiple sclerosis patients, with a decrease in beneficial bacteria and an increase in pro-inflammatory bacteria. Furthermore, changes within the microbial community have been linked to the pathogenesis of Parkinson's disease and Alzheimer's disease. Microbiota-gut-brain communication can impact neurodegenerative diseases through various mechanisms, including the regulation of immune function, the production of microbial metabolites, as well as modulation of host-derived soluble factors. This review describes the current literature on the gut-brain axis and highlights novel communication systems that allow cross-talk between the gut microbiota and the host that might influence the pathogenesis of neuroinflammation and neurodegeneration.

Keywords:  gut–brain-axis; microbial dysbiosis; neurodegenerative diseases

DOI:  https://doi.org/10.3390/ijms241914925
Front Physiol. 2023 ;14 1258540

Cadmium alters whole animal ionome and promotes the re-distribution of iron in intestinal cells of Caenorhabditis elegans.

Anuj Kumar Sharma, Lydia Finney, Stefan Vogt, Olena K Vatamaniuk, Sungjin Kim.

  The chronic exposure of humans to the toxic metal cadmium (Cd), either occupational or from food and air, causes various diseases, including neurodegenerative conditions, dysfunction of vital organs, and cancer. While the toxicology of Cd and its effect on the homeostasis of biologically relevant elements is increasingly recognized, the spatial distribution of Cd and other elements in Cd toxicity-caused diseases is still poorly understood. Here, we use Caenorhabditis elegans as a non-mammalian multicellular model system to determine the distribution of Cd at the tissue and cellular resolution and its effect on the internal levels and the distribution of biologically relevant elements. Using inductively coupled plasma-mass spectrophotometry (ICP-MS), we show that exposure of worms to Cd not only led to its internal accumulation but also significantly altered the C. elegans ionome. Specifically, Cd treatment was associated with increased levels of toxic elements such as arsenic (As) and rubidium (Rb) and a decreased accumulation of essential elements such as zinc (Zn), copper (Cu), manganese (Mn), calcium (Ca), cobalt (Co) and, depending on the Cd-concentration used in the assay, iron (Fe). We regarded these changes as an ionomic signature of Cd toxicity in C. elegans. We also show that supplementing nematode growth medium with Zn but not Cu, rescues Cd toxicity and that mutant worms lacking Zn transporters CDF-1 or SUR-7, or both are more sensitive to Cd toxicity. Finally, using synchrotron X-Ray fluorescence Microscopy (XRF), we showed that Cd significantly alters the spatial distribution of mineral elements. The effect of Cd on the distribution of Fe was particularly striking: while Fe was evenly distributed in intestinal cells of worms grown without Cd, in the presence of Cd, Fe, and Cd co-localized in punctum-like structures in the intestinal cells. Together, this study advances our understanding of the effect of Cd on the accumulation and distribution of biologically relevant elements. Considering that C. elegans possesses the principal tissues and cell types as humans, our data may have important implications for future therapeutic developments aiming to alleviate Cd-related pathologies in humans.

Keywords:  Cadmium; Heavy Metals; XRF; Zinc transporters; copper transporters; ionome; iron

DOI:  https://doi.org/10.3389/fphys.2023.1258540
ACS Chem Neurosci. 2023 Oct 12.

Role of Bmal1 and Gut Microbiota in Alzheimer's Disease and Parkinson's Disease Pathophysiology: The Probable Effect of Melatonin on Their Association.

Mohammad Rafi Khezri, Ayda Esmaeili, Morteza Ghasemnejad-Berenji.

  In recent years, the role of new factors in the pathophysiology of neurodegenerative diseases has been investigated. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases worldwide. Although pathological changes such as the accumulation of aggregated proteins in the brain and inflammatory responses are known as the main factors involved in the development of these diseases, new studies show the role of gut microbiota and circadian rhythm in the occurrence of these changes. However, the association between circadian rhythm and gut microbiota in AD and PD has not yet been investigated. Recent results propose that alterations in circadian rhythm regulators, mainly Bmal1, may regulate the abundance of gut microbiota. This correlation has been linked to the regulation of the expression of immune-related genes and Bmal-1 mediated oscillation of IgA and hydrogen peroxide production. These data seem to provide new insight into the molecular mechanism of melatonin inhibiting the progression of AD and PD. Therefore, this manuscript aims to review the role of the gut microbiota and circadian rhythm in health and AD and PD and also presents a hypothesis on the effect of melatonin on their communication.

Keywords:  Alzheimer’s disease; Bmal1; Parkinson’s disease; gut microbiota; melatonin

DOI:  https://doi.org/10.1021/acschemneuro.3c00418
Int J Mol Sci. 2023 Sep 22. pii: 14421. [Epub ahead of print]24(19):

Cell-Type-Specific Mitochondrial Quality Control in the Brain: A Plausible Mechanism of Neurodegeneration.

Hariprasath Ragupathy, Manasvi Vukku, Sandeep Kumar Barodia.

  Neurodegeneration is an age-dependent progressive phenomenon with no defined cause. Aging is the main risk factor for neurodegenerative diseases. During aging, activated microglia undergo phenotypic alterations that can lead to neuroinflammation, which is a well-accepted event in the pathogenesis of neurodegenerative diseases. Several common mechanisms are shared by genetically or pathologically distinct neurodegenerative diseases, such as excitotoxicity, mitochondrial deficits and oxidative stress, protein misfolding and translational dysfunction, autophagy and microglia activation. Progressive loss of the neuronal population due to increased oxidative stress leads to neurodegenerative diseases, mostly due to the accumulation of dysfunctional mitochondria. Mitochondrial dysfunction and excessive neuroinflammatory responses are both sufficient to induce pathology in age-dependent neurodegeneration. Therefore, mitochondrial quality control is a key determinant for the health and survival of neuronal cells in the brain. Research has been primarily focused to demonstrate the significance of neuronal mitochondrial health, despite the important contributions of non-neuronal cells that constitute a significant portion of the brain volume. Moreover, mitochondrial morphology and function are distinctly diverse in different tissues; however, little is known about their molecular diversity among cell types. Mitochondrial dynamics and quality in different cell types markedly decide the fate of overall brain health; therefore, it is not justifiable to overlook non-neuronal cells and their significant and active contribution in facilitating overall neuronal health. In this review article, we aim to discuss the mitochondrial quality control of different cell types in the brain and how important and remarkable the diversity and highly synchronized connecting property of non-neuronal cells are in keeping the neurons healthy to control neurodegeneration.

Keywords:  astrocytes; microglia; mitochondria; neurons; oligodendrocytes; oxidative stress

DOI:  https://doi.org/10.3390/ijms241914421
Int J Mol Sci. 2023 Sep 28. pii: 14667. [Epub ahead of print]24(19):

Effects of Vitamin E on the Gut Microbiome in Ageing and Its Relationship with Age-Related Diseases: A Review of the Current Literature.

Dashine Gothandapani, Suzana Makpol.

  Ageing is inevitable in all living organisms and is associated with physical deterioration, disease and eventually death. Dysbiosis, which is the alteration of the gut microbiome, occurs in individuals during ageing, and plenty of studies support that gut dysbiosis is responsible for the progression of different types of age-related diseases. The economic burden of age-linked health issues increases as ageing populations increase. Hence, an improvement in disease prevention or therapeutic approaches is urgently required. In recent years, vitamin E has garnered significant attention as a promising therapeutic approach for delaying the ageing process and potentially impeding the development of age-related disease. Nevertheless, more research is still required to understand how vitamin E affects the gut microbiome and how it relates to age-related diseases. Therefore, we gathered and summarized recent papers in this review that addressed the impact of the gut microbiome on age-related disease, the effect of vitamin E on age-related disease along with the role of vitamin E on the gut microbiome and the relationship with age-related diseases which are caused by ageing. Based on the studies reported, different bacteria brought on various age-related diseases with either increased or decreased relative abundances. Some studies have also reported the positive effects of vitamin E on the gut microbiome as beneficial bacteria and metabolites increase with vitamin E supplementation. This demonstrates how vitamin E is vital as it affects the gut microbiome positively to delay ageing and the progression of age-related diseases. The findings discussed in this review will provide a simplified yet deeper understanding for researchers studying ageing, the gut microbiome and age-related diseases, allowing them to develop new preclinical and clinical studies.

Keywords:  age-related disease; ageing; dysbiosis; gut microbiome; vitamin E

DOI:  https://doi.org/10.3390/ijms241914667
J Neurogastroenterol Motil. 2023 Oct 30. 29(4): 409-418

The Effect of Curcumin on the Gut-Brain Axis: Therapeutic Implications.

Ayesheh Enayati, Aida Soghi, Alexandra E Butler, Manfredi Rizzo, Amirhossein Sahebkar.

  The gut-brain axis describes the bidirectional communication between the gut, the enteric nervous system, and the central nervous system. The gut-brain axis has attracted increasing attention owing to its regulatory effect on dysbiosis and a wide range of related diseases. Several types of nutrients, such as curcumin, have been proposed as regulators of the dysbiotic state, and preclinical experiments have suggested that curcumin is not only beneficial but also safe. This review focuses on the interplay between curcumin and the gut microbiota. Moreover, it provides a comprehensive review of the crosstalk between the gut-brain axis and disease, whilst also discussing curcumin-mediated gut-brain axis-dependent and -independent signaling about modulation of gut microbiota dysbiosis. This will help to define the utility of curcumin as a novel therapeutic agent to regulate intestinal microflora dysbiosis.

Keywords:  Curcumin; Dysbiosis; Gut microbiota; Gut-Brain axis; Health

DOI:  https://doi.org/10.5056/jnm23065
Aquat Toxicol. 2023 Sep 29. pii: S0166-445X(23)00312-0. [Epub ahead of print]264 106710

Exposure to epoxy-modified nanoplastics in the range of μg/L causes dysregulated intestinal permeability, reproductive capacity, and mitochondrial homeostasis by affecting antioxidant system in Caenorhabditis elegans.

Man Qu, Yuhan An, Xinyi Jiang, Qinlin Wu, Long Miao, Xing Zhang, Yang Wang.

  Although surface chemically modified nanopolystyrene (PS) has been reported to have potential toxicity toward organisms, the impact of epoxy modification on the toxicity of PS remains largely unknown. In this study, we first investigated the prolonged exposure effects of epoxy-modified PS (PS-C2H3O) in the range of μg/L on Caenorhabditis elegans (C. elegans) including general toxicity, target organ toxicity, and organelle toxicity. Our data revealed that C. elegans exposed to PS-C2H3O led to the alterations in increased lethality (≥ 1000 μg/L), shortened body length (≥ 100 μg/L), and decreased locomotion capacity (≥ 1 μg/L). In addition, toxicity analysis on target organs and organelles indicated that exposure to PS-C2H3O enhanced intestinal permeability (≥ 100 μg/L) by inhibiting the transcriptional levels of acs-22 (encoding fatty acid transport protein) (≥ 100 μg/L) and hmp-2 (encoding α-catenin) (≥ 1000 μg/L), reduced reproductive capacity (≥ 10 μg/L), and dysregulated mitochondrial homeostasis (≥ 1 μg/L). Moreover, the activation of antioxidant enzyme system could help nematodes against the toxicity caused by PS-C2H3O exposure (≥ 10 μg/L). Furthermore, we also compared the toxicity of PS-C2H3O with other chemically modified derivatives of PS, and the toxicity order was PS-NH2 > PS-SOOOH > PS-C2H3O > PS-COOH > PS > PS-PEG. Our study highlights the potential environmental impact of PS and its derivatives on organisms and suggests that the toxicity of nanoplastics may be charge-dependent.

Keywords:  C. elegans; Epoxy-modification; Long-term exposure; Nanoplastics; Toxicity

DOI:  https://doi.org/10.1016/j.aquatox.2023.106710