The impact of maternal diabetes on the future health and neurodevelopment of the offspring: a review of the evidence

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: July 3, 2023

Maternal health during gestational period is undoubtedly critical in shaping optimal fetal development and future of the offspring. Gestational diabetes mellitus a metabolic disorder occurring pregnancy with an alarming increasing incidence worldwide recent years. Over years, there growing body evidence that uncontrolled maternal hyperglycaemia can potentially have detrimental effect on neurodevelopment Both human animal data linked motor cognitive impairment, as well autism spectrum disorders, attention deficit hyperactivity disorder, learning abilities psychiatric disorders. This review presents available from current literature investigating relationship between offspring neurodevelopmental impairment. Moreover, possible mechanisms accounting for effects brain like neuroinflammation, iron deficiency, epigenetic alterations, disordered lipid metabolism structural abnormalities are also highlighted. On basis demonstrated literature, it mandatory will be optimally controlled impact more thoroughly investigated.

Language: Английский

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AdipoRon’s Impact on Alzheimer’s Disease—A Systematic Review and Meta-Analysis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 484 - 484

Published: Jan. 8, 2025

Alzheimer's disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, neuroinflammation. Despite advancements in early detection, diagnosis, treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, the limited efficacy current therapies. Consequently, there is pressing need for novel therapeutic agents target multifaceted aspects enhance treatments, minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, mitigating tau hyperphosphorylation. This review aimed evaluate effects AdipoRon-based replacement therapy against AD, using comprehensive approach grounded PICO framework-Population, Intervention, Comparison, Outcomes. A total six studies were reviewed, vitro vivo investigations examining AdipoRon's impact on various models. These involved different cell lines transgenic mouse models, assessing outcomes such as phosphorylation, relevant molecular pathways. By synthesizing data from these studies, our thoroughly explains mechanisms action, agent AD. analysis aims highlight state knowledge, identify gaps research, suggest directions future clinical applications.

Language: Английский

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Effects of dietary restriction on neuroinflammation in neurodegenerative diseases

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(2)

Published: Jan. 8, 2021

Recent and accumulating work in experimental animal models humans shows that diet has a much more pervasive prominent role than previously thought modulating neuroinflammatory neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction profound effects shaping brain peripheral metabolism, immunity, gut microbiome biology. Interactions among calorie intake, meal frequency, quality, modulate specific metabolic molecular pathways regulate cellular, tissue, organ homeostasis as well inflammation during normal aging CNS diseases, including Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, multiple others. This review discusses these findings their potential application prevention treatment diseases promotion healthy aging.

Language: Английский

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Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: June 29, 2023

Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, the relationship between these is bidirectional. The association depression highly co-morbid tends to significantly exacerbate metabolic related depressive symptoms. However, neural mechanism under mutual control of largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain vivo homeostatic regulation link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation well neuroendocrine regulators energy metabolism including adipocytokines lipokines. In addition, summarizes potential future treatments for raises several questions need be answered research. will provide a comprehensive description localization biological connection better understand co-morbidity depression.

Language: Английский

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The mind–skin connection: A narrative review exploring the link between inflammatory skin diseases and psychological stress

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2024, Volume and Issue: 38(5), P. 821 - 834

Published: Feb. 4, 2024

Abstract Inflammatory skin diseases are known to negatively impact patient psychology, with individuals experiencing higher rates of stress and subsequent diminished quality life, as well mental health issues including anxiety depression. Moreover, increased psychological has been found exacerbate existing inflammatory diseases. The association between is a timely topic, framework better understand the relationship two that integrates available literature needed. In this narrative review article, we discuss potential neurobiological mechanisms behind due diseases, focusing mainly on proinflammatory cytokines in circulating system (the brain‐gut‐skin communications) default mode network brain. We also descending pathways from brain lead aggravation stress, central peripheral hypothalamic–pituitary–adrenal axes, nerves barrier function.

Language: Английский

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International Symposium on Ruminant Physiology: The immunometabolism of transition dairy cows from dry-off to early lactation: lights and shadows

Journal of Dairy Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The mismatch between the nutrient intake from diet and output by mammary gland causes a negative energy balance in transition dairy cows, that, if excessive, can promote several metabolic disorders. Other relevant phenomena occur during transition, such as inflammation at calving changes immunocompetence, redox balance, mineral metabolism. Despite efforts, some aspects of adaptive mechanisms observed period still need to be clarified. For instance, alterations physiological responses even before dry-off or dry affect success whole certain cows. In this context, mechanism regulating inflammatory response around may play pivotal role, suggested variety factors influencing it its consequences, particularly feed depression, that amplify anticipate balance. When derails is unclear, but detecting triggers diverted abnormal where they stem (e.g., liver, rumen gut epithelia, uterus, gland) will help discover weak points immune system possible ways restoring it. Furthermore, postpartum healthy cow appears have an acute phase liver level, despite decrease circulating proinflammatory cytokines. What what pathological context? To understand latter, finding markers unsuccessful go beyond deficit would advisable. Future efforts should dedicated clarifying calving, exploiting potential biology. Moreover, helpful, for both basic applied research, define biomarkers associated with (i.e., cytokines proteins) introduce genetic selection phenotypes related ability cows adapt immunometabolic stress typical period.

Language: Английский

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Improving brain health via the central executive network

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Cognitive and physical stress have significant effects on brain health, particularly through their influence the central executive network (CEN). The CEN, which includes regions such as dorsolateral prefrontal cortex, anterior cingulate cortex inferior parietal lobe, is to managing demands of cognitively challenging motor tasks. Acute can temporarily reduce connectivity within leading impaired cognitive function emotional states. However a rebound in these states often follows, driven by motivational signals mesocortical mesolimbic pathways, help sustain inhibitory control task execution. Chronic exposure challenges leads long‐term improvements CEN functionality. These changes are supported neurochemical, structural systemic adaptations, including mechanisms tissue crosstalk. Myokines, adipokines, anti‐inflammatory cytokines gut‐derived metabolites contribute biochemical environment that enhances neuroplasticity, reduces neuroinflammation supports neurotransmitters serotonin dopamine. processes strengthen connectivity, improve self‐regulation enable individuals adopt health‐optimizing behaviours. Long‐term activity not only but also risk age‐related decline neurodegenerative diseases. This review highlights role progressive exercise practical approach strengthening promoting offering strategy resilience well‐being across lifespan. image

Language: Английский

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An optimized quantitative proteomics method establishes the cell type‐resolved mouse brain secretome

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(20)

Published: Sept. 21, 2020

Resource21 September 2020Open Access Source DataTransparent process An optimized quantitative proteomics method establishes the cell type-resolved mouse brain secretome Johanna Tüshaus orcid.org/0000-0001-9206-8093 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University Search more papers by this author Stephan A Müller Evans Sioma Kataka Department Bioinformatics, Wissenschaftszentrum Weihenstephan, Freising, Jan Zaucha Laura Sebastian Monasor Minhui Su orcid.org/0000-0001-5803-6098 Institute Neuronal Cell Biology, Gökhan Güner Georg Jocher Sabina Tahirovic orcid.org/0000-0003-4403-9559 Dmitrij Frishman Mikael Simons Munich Cluster Systems Neurology (SyNergy), Stefan F Lichtenthaler Corresponding Author [email protected] orcid.org/0000-0003-2211-2575 Information Tüshaus1,2, Müller1,2, Kataka3, Zaucha3, Monasor1, Su1,4, Güner1,2, Jocher1,2, Tahirovic1, Frishman3, Simons1,4,5 and *,1,2,5 1German 2Neuroproteomics, 3Department 4Institute 5Munich *Corresponding author. Tel: +49 89 440046425; E-mail: The EMBO Journal (2020)39:e105693https://doi.org/10.15252/embj.2020105693 PDFDownload PDF article text main figures. Peer ReviewDownload a summary editorial decision including letters, reviewer comments responses to feedback. ToolsAdd favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract To understand how cells communicate in nervous system, it is essential define their secretome, which challenging primary because large numbers being required. Here, we miniaturized analysis developing "high-performance protein enrichment with click sugars" (hiSPECS) method. demonstrate its broad utility, hiSPECS was used identify secretory response slices upon LPS-induced neuroinflammation establish resource using astrocytes, microglia, neurons, oligodendrocytes. This allowed mapping cellular origin CSF proteins revealed that an unexpectedly high number secreted vitro vivo are proteolytically cleaved membrane ectodomains. Two examples neuronally ADAM22 CD200, identified as substrates Alzheimer-linked protease BACE1. can be widely exploited systematically study secretion function type-specific biomarkers CNS diseases. Synopsis proteomic miniaturizes resource. enabled from under neuroinflammatory conditions. presence serum proteins. cell-type resolved includes oligodendrocytes cortical versus hippocampal neurons. Proteolytic shedding major mechanism secretion. allows LPS stimulation. identifies CD200 new Introduction Protein inter-cellular communication tissue homeostasis multicellular organisms has central role development, function, maintenance, inflammation system. Proteins referred comprise soluble proteins, such insulin, granulins, APOE, extracellular matrix (e.g., neurocan, fibronectin). also comprises domains e.g., growth factors, cytokines, receptors, adhesion neuregulin, NCAM, N-cadherin), generated mostly membrane-bound proteases called ectodomain (Lichtenthaler et al, 2018). However, largely unknown what extent contributes total differs between types brain. Omics' approaches have collections mRNA abundance data across different Zhang 2014; Sharma 2015). In contrast, little known about whether—in parallel expression types—they multiple or instead manner vitro, ex organotypic slice culture), vivo. Cerebrospinal fluid (CSF) constitutes easily accessible body studying (patho-)physiology measuring identifying disease (Olsson 2016; Johnson 2020; Zetterberg Bendlin, 2020), but type from, no systematic studies available. Dysregulated linked neurologic psychiatric diseases, neurodegeneration, APP, SORL1, TREM2 Alzheimer's (AD), prion (PRNP) Thus, identification quantification secretomes do not only allow understanding biological processes physiological conditions, contribute unraveling molecular basis diseases drug targets biomarkers, shed AD (Suarez-Calvet Ewers 2019; Schindler 2019). Systematic commonly done conditioned medium (primary) mass spectrometry-based proteomics. challenge low concentration within (Schira-Heinen Therefore, many concentrate tens millions (Kleifeld 2010, 2011; Kuhn 2012; Wiita Schlage often available cells, where on average one million may purified individual adult mice. methods second dynamic range secretomes, particular when cultured serum-like supplements, highly abundant (most notably albumin), hampering detection endogenous, cell-derived whose levels typically orders magnitude lower (Eichelbaum 2012). serum- protein-free starvation conditions 2010; Meissner 2013; Deshmukh 2015), which, however, strongly alter composition induce death alternative approach, compatible culture metabolically label exogenous analogs methionine sugars incorporated into backbone glycan structures, newly synthesized respectively even these established still require extensive fractionation, either at level peptide 2012) and, thus result laborious sample preparation, spectrometry measurement times, requirement amounts samples, tissues. developed method, down-scales speeds up now single mice We applied determine Broad applicability demonstrated (i) gaining insights shedding; (ii) BACE1, target AD; (iii) determining CSF; (iv) revealing inflammatory lead systemic slices. Results Development benchmarking against SPECS enable (i.e., supplements), previously required 40 per experiment (Kuhn introduced four changes (Fig 1A; see Fig EV1A detailed comparison SPECS). First, after labeling N-azido-mannosamine (ManNAz), azido group-bearing sugar, glycoproteins were enriched lectin-based precipitation concanavalin (ConA). reduced albumin, glycoprotein EV1B). Because majority most proteins—which through shedding—are glycosylated 2016), fraction Second, selectively captured azido-glycoproteins covalent binding magnetic dibenzylcyclooctyne (DBCO)–alkyne beads copper-free chemistry. stringent washing reduce contaminating Third, on-bead digestion performed release tryptic peptides label-free (LFQ). Fourth, measurements Q Exactive HF spectrometer data-dependent acquisition (DDA) recently data-independent (DIA) (Bruderer 2015; Gillet Ludwig 2018; EV1C). DDA DIA two modes acquired. contrast DDA, limited subsequent sequencing identification, fragments, detects all defined m/z window, particularly advantageous (Gillet Bruderer 2020). benchmark previous protocol, collected murine neurons supplement before 2012), (40-fold fewer compared Despite miniaturization, quantified 186% 236% modes, respectively, dataset (according UniProt glycoproteomic studies; Figs 1B EV1D E; Table EV1) (Zielinska Fang Liu 2017; Joshi Furthermore, provided 18% 11% transmembrane 1C). Overall, extended almost order magnitude, evaluated based intensity-based absolute (iBAQ) values representing rough estimate molar abundances (Schwanhäusser 1D). Due superiority over regard proteome coverage reproducibility analysis, focused throughout manuscript. 99.9% (2,273/2,276) unique single-pass mapped predicted important quality control, demonstrates contains ectodomains full-length reliably secretome-specific 1E). Figure 1. Workflow Graphical illustration workflow. Cells labeled metabolized azido-sialic acid N- O-linked glycans glycoproteins, exogenously added ACN: acetonitrile. Bar chart indicating quantification, localization UniProt) comparing (blue) (light green) (dark green). counted if least 9 11 replicates 4 5 paper category glycoprotein* annotations annotated annotations, APP membrane, TM, cytoplasm, nucleus, distinct proteolytic fragments found organelles, so some categories cytoplasm nucleus overlap TM + GPI. IDs: Venn diagram groups (5/6 replicates) same samples. Left panel: glycoprotein. Right GPI potentially Distribution (at 3 6 replicates). plotted log10-transformed bin size 0.5. iBAQ roughly correlate difference log10 scale represents 10-fold difference. indicated light dark green, respectively. colored purple, All onto domains. Only 0.1% intracellular domains, demonstrating ectodomains, forms Comparison number, volume media, preparation time, time. Data information: TM: protein; GPI: glycosylphosphatidylinositol-anchored protein. Download figure PowerPoint Click here expand figure. EV1. Benchmarking novel (green) protocol uses followed improves processing. On-bead (LFQ) (DIA vs DDA). depends biotinylation azide-functionalized streptavidin pull-down, SDS-gel-based fractionation 14 gel slices, only. Coomassie-stained showing prominent reduction albumin ConA. lane: (conditioned medium) enrichment. 10% loaded ConA eluate beads. band highlighted red arrow. representative density plot neuronal analyzed mode. ratio retention One MS1 scan (purple) 20 MS2 scans covering 300–1,400 1 adjoining windows. windows adjusted achieve equal peptides. Identified according UniProt, (Fang (Joshi 2018), (Liu 2017), 2010). illustrating sources (D) contain glycosylation site. As expected glyco-secretome, than 85% glycoproteins. Representative Pearson correlations log2-transformed LFQ intensities (BR) processed studies, pairs separated reproducibility, whereas correlation run gels rather low. ratios statistical evaluation. blue squares indicate samples during [SPECS obtained 2012)]. procedure does further fractionation. time both fivefold times 1F). Importantly, improved among replicates, reflected coefficient 0.97 0.84 EV1F). Taken together, outperforms sensitivity, coverage, Secreted key roles signal transduction, unclear they expressed types. manner, focusing types—astrocytes, 2A; EV2, Appendix S1). each prepared brains. For detected five out six type. yielded 995 microglia having largest (753) astrocytes smallest (503) 2B). GO compartment region term underlining our library EV2A B). additional control measure type-specifically marker LINGO1, SEZ6, L1CAM EV2C). 111 2C) (Sharma EV3), > 10,000 lysates types, had been taken (Table EV2). CPN1, TIMP1) ADAM19, CRIM1, FRAS1) GALNT18, assumed pseudogene Together, complementary lysate whole organ. 2. Illustration oligodendrocytes, cerebrospinal (hippocampus (Hip), cortex (Ctx)). Number (left) (right) investigated considered. total, detected. (ID) gray part column indicates reveals secretome. Relative covered (gray), annotation (15%) (lower panel). Correlation relationship shows (red higher, correlation) plots log2 UMAP (Uniform Manifold Approximation Projection) segregation percentage graph groups, one, two, three, replicates. EV2. Quality transformation Log2 (N = 1). median, boxes upper quartile, whiskers minimum maximum, dots outliers. Functional clustering DAVID 6.8 (da Huang 2009a; da 2009b) gene ontology component (FAT) background. dot sizes score. Fold change cells. specific median other 2015) shown. Known strong verifying comparability cultures. example, NCAM2 (with y-axis value scale) eightfold three higher Horizontal lines mean. Principal (PCA). segregated components al

Language: Английский

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Adiponectin modulates ventral tegmental area dopamine neuron activity and anxiety-related behavior through AdipoR1

Molecular Psychiatry, Journal Year: 2018, Volume and Issue: 24(1), P. 126 - 144

Published: July 9, 2018

Adiponectin, a metabolic hormone secreted by adipocytes, can cross the blood–brain barrier to act on neurons in different brain regions, including those involved stress-related disorders. Here we show that dopamine ventral tegmental area (VTA) express adiponectin receptor 1 (AdipoR1). Intra-VTA infusion of or mimetic AdipoRon wild-type mice decreases basal neuron population activity and firing rate reverses restraint stress-induced increase anxiety behavior. Adiponectin haploinsufficiency leads increased behavior under conditions. Ablation AdipoR1 specifically from enhances neuronal anxiogenic responses stress. The effects intra-VTA were abolished lacking neurons. These observations indicate directly modulate VTA behavior, is required for adiponectin-induced inhibition anxiolytic effects. results strengthen idea as key biological factor links syndrome emotional

Language: Английский

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<p>Atypical antipsychotics-induced metabolic syndrome and nonalcoholic fatty liver disease: a critical review</p>

Neuropsychiatric Disease and Treatment, Journal Year: 2019, Volume and Issue: Volume 15, P. 2087 - 2099

Published: July 1, 2019

Abstract: The atypical antipsychotics (AAPs) have been used as first-line drugs in psychiatric practice for a wide range of psychotic disorders, including schizophrenia and bipolar mania. While effectively exerting therapeutic effects on positive negative symptoms, well cognitive impairments patients, these are less likely to induce extrapyramidal symptoms compared typical antipsychotics. However, the increasing application them has raised questions their tolerability adverse over endocrine, metabolic, cardiovascular axes. Specifically, AAPs associated different extents, with weight gain, metabolic syndrome (MetS), nonalcoholic fatty liver disease (NAFLD). This article summarized clinical evidence showing side patients schizophrenia, experimental AAPs-induced observed animals cell culture studies. In addition, it discussed potential mechanisms involved APPs-induced MetS NAFLD. Keywords: antipsychotics, MetS, NAFLD,

Language: Английский

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