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- Venero, J. L., et al.
(författare)
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ARG1 expression in basal forebrain microglia modulates hippocampal innervation and cognition during postnatal development
- 2023
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Ingår i: Glia. - : John Wiley & Sons. - 0894-1491 .- 1098-1136. ; 71:Suppl. 1, s. E512-E512
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e.Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+microgliacontain cellular inclusions and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.
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| 3. |
- Madrigal-Ruiz, P. M., et al.
(författare)
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The unbalance of adiponectin oligomers, RvE1 and chemerin levels are associate with increase of adiposopathy status and insulin resistance in obesity
- 2019
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Ingår i: Journal of Translational Science. - : Open Access Text. - 2059-268X. ; 5
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The aim was to establish if the balance adiponectin-oligomers, resolvin-E1 and chemerin levels could contribute to the insulin resistance (IR) setting of subjects with obesity, based on their serum levels and its relationship with inflammatory markers, metabolic profile and adiposopathy status.Methods: This study included 230 individuals, classified according to World Health Organization criteria by body mass index (BMI) kg/m2 in two groups: without-obesity (from 18.5 to 29.9) and with-obesity (from 30.0 to 39.9). Body fat mass distribution, metabolic and inflammatory markers were measured by anthropometric, enzymatic and immuno-turbidimetry methods, respectively. Serum insulin, resolvin-E1, chemerin, and adiponectin-oligomers were evaluating by ELISA method. Analysis performed were correlations IR-indexes with adiposity, receiver operating characteristic (ROC) curves and the adiponectin-oligomers, resolvin-E1 and chemerin tertiles.Results: Subjects’ with-obesity showed adiposopathy status, characterized by metabolic dysregulation and a subclinical inflammatory profile. They presented higher levels (`x ±SD, ng/mL) of resolvin-E1 (1227 ±668 versus 909 ±769, P= 0.017), chemerin (91 ±31 versus 79 ±23, P= 0.013) and LMW-Adiponectin (2257 ±797 versus 1030 ±1055, P= 0.011), whereas HMW-Adiponectin was lower (2470 ±1095 versus 3236 ±1848, P= 0.010), compared to the without-obesity individuals. Individuals’ with-obesity also displayed positive correlation of IR markers (rho from 0.163 to 0.479) along body fat measurements, metabolic and inflammation profiles. Moreover, a negative correlation of HMW-Adiponectin (rho from –0.564 to –0.214) with body fat measurements, metabolic and inflammation profiles. IR-indexes, LMW-Adiponectin and resolvin-E1/chemerin relationship showed differences between groups’ with-obesity and without-obesity, but not with gender. ROC curves shown potential ability of the LMW-Adiponectin levels to differentiate IR from non-IR individuals, with AUC of 0.815, P<0.0001 (95%, CI: 0.726-0.903).Conclusion: The present study shown that LMW-Adiponectin-resolvinE1-chemerin serum unbalance establishes a specific relationship with adiposopathy in individuals with obesity, which could be a way to identify risk factors in early stages of IR.
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| 4. |
- Stratoulias, Vassilis, et al.
(författare)
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ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain
- 2023
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 26:6, s. 1008-1020
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Tidskriftsartikel (refereegranskat)abstract
- Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1- microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.
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| 6. |
- Fazel, Seena, et al.
(författare)
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Risk of death by suicide following self-harm presentations to healthcare : development and validation of a multivariable clinical prediction rule (OxSATS)
- 2023
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Ingår i: BMJ Mental Health. - : BMJ Publishing Group Ltd. - 2755-9734. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes. OBJECTIVE: We developed and validated a predictive model for suicide following self-harm.METHODS: We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work.FINDINGS: An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS).CONCLUSIONS: OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility.CLINICAL IMPLICATIONS: Using a clinical prediction score may assist clinical decision-making and resource allocation.
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| 7. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Dynamics of the human gut microbiome in inflammatory bowel disease
- 2017
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Ingår i: Nature Microbiology. - London, United Kingdom : Nature Publishing Group. - 2058-5276. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is characterized by flares of inflammation with a periodic need for increased medication and sometimes even surgery. The aetiology of IBD is partly attributed to a deregulated immune response to gut microbiome dysbiosis. Cross-sectional studies have revealed microbial signatures for different IBD subtypes, including ulcerative colitis, colonic Crohn's disease and ileal Crohn's disease. Although IBD is dynamic, microbiome studies have primarily focused on single time points or a few individuals. Here, we dissect the long-term dynamic behaviour of the gut microbiome in IBD and differentiate this from normal variation. Microbiomes of IBD subjects fluctuate more than those of healthy individuals, based on deviation from a newly defined healthy plane (HP). Ileal Crohn's disease subjects deviated most from the HP, especially subjects with surgical resection. Intriguingly, the microbiomes of some IBD subjects periodically visited the HP then deviated away from it. Inflammation was not directly correlated with distance to the healthy plane, but there was some correlation between observed dramatic fluctuations in the gut microbiome and intensified medication due to a flare of the disease. These results will help guide therapies that will redirect the gut microbiome towards a healthy state and maintain remission in IBD.
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| 8. |
- Martín-Márquez, BT, et al.
(författare)
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Osteopontin : another piece in the systemic lupus erythematosus immunopathology puzzle
- 2022
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Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 40:1, s. 173-182
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Forskningsöversikt (refereegranskat)abstract
- Osteopontin (OPN) is a phosphoglycoprotein involved in bone remodelling, wound healing, cell adhesion, tissue remodelling, and immune response that is distributed widely in normal adult tissues. OPN biological activity is regulated by thrombin and matrix metalloproteinases (MMPs) cleavage, where the full-length (OPN-FL) protein and the cleaved OPN-N are associated with autoimmune diseases such as systemic lupus erythematosus (SLE). OPN overexpression has been associated with a predisposition to SLE and bad prognosis since OPN could mediate a sustained polyclonal B cell activation that besides to intracellular OPN (iOPN) form, promote the T follicular helper (T-FH) cells and enhance anti-nuclear antibody production. Currently, the role of OPN in lupus nephritis (LN) has been reported and extensively studied; however, no data are available about the potential mechanism of OPN in neuropsychiatric SLE (NPSLE). In this review, we highlighted the contribution of OPN and iOPN in LN and NPSLE immunopathology.
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| 9. |
- Martínez-Sánchez, Noelia, et al.
(författare)
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Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
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