| 1. |
- Falk Erhag, Hanna, et al.
(författare)
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A Multidisciplinary Approach to Capability in Age and Ageing
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This open access book provides insight on how to interpret capability in ageing – one’s individual ability to perform actions in order to reach goals one has reason to value – from a multidisciplinary approach. With for the first time in history there being more people in the world aged 60 years and over than there are children below the age of 5, the book describes this demographic trends as well as the large global challenges and important societal implications this will have such as a worldwide increase in the number of persons affected with dementia, and in the ratio of retired persons to those still in the labor market. Through contributions from many different research areas, it discussed how capability depends on interactions between the individual (e.g. health, genetics, personality, intellectual capacity), environment (e.g. family, friends, home, work place), and society (e.g. political decisions, ageism, historical period). The final chapter by the editors summarizes the differences and similarities in these contributions. As such this book provides an interesting read for students, teachers and researchers at different levels and from different fields interested in capability and multidisciplinary research.
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| 2. |
- Solinas, Giovanni, et al.
(författare)
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An adipoincretin effect links adipostasis with insulin secretion.
- 2024
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Ingår i: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
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Forskningsöversikt (refereegranskat)abstract
- The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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| 3. |
- Bauzá-Thorbrügge, Marco, et al.
(författare)
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NRF2 is essential for adaptative browning of white adipocytes.
- 2023
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Ingår i: Redox biology. - : Elsevier. - 2213-2317. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes.
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| 4. |
- Molinaro, Angela, et al.
(författare)
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Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS.
- 2019
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 29:6
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Tidskriftsartikel (refereegranskat)abstract
- Phosphatidylinositol-3-kinase (PI3K) activity is aberrant in tumors, and PI3K inhibitors are investigated as cancer therapeutics. PI3K signaling mediates insulin action in metabolism, but the role of PI3K isoforms in insulin signaling remains unresolved. Defining the role of PI3K isoforms in insulin signaling is necessary for a mechanistic understanding of insulin action and to develop PI3K inhibitors with optimal therapeutic index. We show that insulin-driven PI3K-AKT signaling depends on redundant PI3Kα and PI3Kβ activities, whereas PI3Kδ and PI3Kγ are largely dispensable. We have also found that RAS activity promotes AKT phosphorylation in insulin-stimulated hepatocytes and that promotion of insulin-driven AKT phosphorylation by RAS depends on PI3Kα. These findings reveal the detailed mechanism by which insulin activates AKT, providing an improved mechanistic understanding of insulin signaling. This improved model for insulin signaling predicts that isoform-selective PI3K inhibitors discriminating between PI3Kα and PI3Kβ should bedosed below their hyperglycemic threshold to achieve isoform selectivity.
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| 5. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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Long-term potentiation and insult conditioning in hippocampal slices from young rats: a role for protein synthesis under chemical stress?
- 2010
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Ingår i: The 10th Biennial Meeting of the Asia-Pacific Society for Neurochemistry (APSN), October 17-20, 2010, Phuket, Thailand.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We have previously demonstrated that in young rats (12-20-day-old) a sustained long-term potentiation (LTP) can still be induced under conditions of protein synthesis inhibition. It was therefore suggested that sufficient and necessary proteins were already available at the induction time to accomplish LTP maintenance for several hours. Against this background, we have questioned whether hippocampal slices subjected to certain insult conditions might be more sensitive to protein synthesis inhibitors. High K+ concentration has previously been reported to cause an amnesic effect in vivo as well as increasing protein turnover in vitro. We have here employed a K+ insult model under conditions when protein synthesis was inhibited. Recordings were obtained from hippocampal slices for up to 9 h, with or without a cocktail of protein synthesis inhibitors, containing cycloheximide (60 µM) and anisomycin (25 µM). High potassium (50 mM) was transiently applied (5-15 min) shortly after inducing LTP in one of two separate pathways stimulated alternatively. Additionally, an NMDA-receptor antagonist AP5 was supplied after LTP induction to minimize effects related to depolarization-induced glutamate release. Following elimination of all responses for about 30 min, both test and control responses partly recovered. The degree of remaining LTP, defined as test/control ratio, was reduced in both groups of slices (NMDA-independent depotentiation) but was significantly smaller in the drug-treated ones. We are also running an insult model based on oxidative stress, applying hydrogen peroxide (4-5 mM) before or after LTP induction; however, the results are still insufficient for a final conclusion. The potency of cycloheximide, anisomycin or cocktail of the drugs was verified by measurement of incorporation of [3H]-leucine into trichloracetic acid (TCA) precipitable macromolecules. Cycloheximide, anisomycin or cocktail, at concentrations used here caused 95%, 97% and 95% blocking effect, respectively. Our data confirm the idea that sufficient and necessary constitutive proteins are available in the young hippocampus to maintain LTP under conditions of protein synthesis inhibition. They also reveal that LTP in slices subjected to certain insult conditions early after the induction is sensitive to protein synthesis inhibition, probably due to increase in constitutive proteins turnover.
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| 6. |
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| 7. |
- Khoshnood, Ardavan
(författare)
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Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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| 8. |
- Andersson, Christin, et al.
(författare)
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Increasing CSF phospho-tau levels during cognitive decline and progression to dementia
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:10, s. 1466-1473
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about longitudinal changes of cerebrospinal fluid (CSF) biomarkers during cognitive decline in neurodegenerative disease progression. OBJECTIVE: To investigate longitudinal changes in CSF biomarkers--total-tau (T-tau), phospho-tau (P-tau) and beta-amyloid (Abeta42)--during cognitive decline. METHODS: Forty memory clinic patients (47.5% females), aged 61.3+/-7.6 (S.D.) years, non-demented at baseline, underwent lumbar puncture and neuropsychological testing at two occasions. Baseline mean MMSE-score was 28.3+/-1.8. Patients were divided into three groups based on baseline memory functioning; severely impaired (SIM), moderately impaired (MIM) and no impairment (NIM). RESULTS: There was a significant increase in P-tau in the SIM-group during follow-up, while P-tau in MIM and NIM did not change. Eighty-three percent of the SIM-patients converted to dementia (80% AD), while most MIM- and NIM-patients remained non-demented. T-tau- and Abeta42-levels did not change in any of the memory groups during follow-up. CONCLUSION: Increasing P-tau levels during cognitive decline and conversion to dementia suggest that P-tau may be useful as a longitudinal marker of the neurodegenerative process.
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| 9. |
- Andersson, Ingemar, 1950-
(författare)
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Rehabilitering vid långvarig smärta
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 401-409
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Elcadi, Guilherme H., 1966-, et al.
(författare)
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Shoulder and forearm oxygenation and myoelectric activity in patients with work related muscle pain and healthy subjects
- 2013
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Ingår i: European Journal of Applied Physiology. - New York : Springer. - 1439-6319 .- 1439-6327. ; 113:5, s. 1103-1115
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Tidskriftsartikel (refereegranskat)abstract
- We tested hypotheses of (i) reduced oxygen usage, oxygen recovery, blood flow and oxygen consumption; and (ii) increased muscle activity for patients diagnosed with work related muscle pain in comparison to healthy controls. Oxygenation was measured with near infrared spectroscopy (NIRS), and muscle activity with EMG for the extensor carpi radialis (ECR) and trapezius descendens (TD) muscles. Eighteen patients with diffuse neck-shoulder-arm pain and seventeen controls (matched in age and sex) were equipped with NIRS and EMG probes. After determining an individual’s maximum voluntary contraction (MVC) force, short term (20 sec) isometric contractions for the ECR and TD of 10%, 30%, 50% and 70% MVC generated ∆StO2% and StO2% recovery (Rslope) from NIRS, and RMS%max from EMG signals. In addition, upper arm venous (VO) and arterial (AO) occlusions generated slopes of total hemoglobin (HbTslope) and deoxyhemoglobin (HHbslope) for the resting ECR as surrogates of blood flow and oxygen consumption, respectively. Mixed Model analyses, t-tests, and Mann-Whitney test were used to assess differences between groups. There was no significant difference in MVC between groups for either muscle. Also, ∆StO2%, Rslope for either muscle, and ECR-HbTslope were not different between groups, thus our hypotheses of reduced oxygen use, recovery, and blood flow for patients were not confirmed. However, patients had a significantly lower ECR-HHbslope confirming our hypothesis of reduced consumption. Further, there was no difference in RMS%max during contractions meaning that the hypothesis of increased activity for patients was not confirmed. When taking into account the number of NIRS variables studied, differences we found between our patient group and healthy controls (i.e. in forearm oxygen consumption and shoulder oxygen saturation level) may be considered modest. Overall our findings may have been impacted by the fact that our patients and controls were similar in muscle strength, which is in contrast to previous studies.
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| 11. |
- Fransén, Karin, 1973-, et al.
(författare)
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CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study
- 2022
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Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females.Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported.Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p < 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026).Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.
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| 12. |
- Nowak, Christoph, 1986-
(författare)
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Insulin Resistance : Causes, biomarkers and consequences
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The worldwide increasing number of persons affected by largely preventable diseases like diabetes demands better prevention and treatment. Insulin is required for effective utilisation of circulating nutrients. Impaired responsiveness to insulin (insulin resistance, IR) is a hallmark of type 2 diabetes and independently raises the risk of heart attack and stroke. The pathophysiology of IR is incompletely understood. High-throughput measurement of large numbers of circulating biomarkers may provide new insights beyond established risk factors.The aims of this thesis were to (i) use proteomics, metabolomics and genomics methods in large community samples to identify biomarkers of IR; (ii) assess biomarkers for risk prediction and insights into aetiology and consequences of IR; and (iii) use Mendelian randomisation analysis to assess causality.In Study I, analysis of 80 circulating proteins in 70-to-77-year-old Swedes identified cathepsin D as a biomarker for IR and highlighted a tentative causal effect of IR on raised plasma tissue plasminogen activator levels. In Study II, nontargeted fasting plasma metabolomics was used to discover 52 metabolites associated with glycaemic traits in non-diabetic 70-year-old men. Replication in independent samples of several thousand persons provided evidence for a causal effect of IR on reduced plasma oleic acid and palmitoleic acid levels. In Study III, nontargeted metabolomics in plasma samples obtained at three time points during an oral glucose challenge in 70-year-old men identified associations between a physiologic measure of IR and concentration changes in medium-chain acylcarnitines, monounsaturated fatty acids, bile acids and lysophosphatidylethanolamines. Study IV provided evidence in two large longitudinal cohorts for causal effects of type 2 diabetes and impaired insulin secretion on raised coronary artery disease risk.In conclusion, the Studies in this thesis provide new insights into the pathophysiology and adverse health consequences of IR and illustrate the value of combining traditional epidemiologic designs with recent molecular techniques and bioinformatics methods. The results provide limited evidence for the role of circulating proteins and small molecules in IR and require replication in separate studies and validation in experimental designs.
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| 13. |
- Turanli, Beste, et al.
(författare)
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Drug Repositioning for Effective Prostate Cancer Treatment
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.
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| 14. |
- Crommert, Martin Eriksson, 1974-, et al.
(författare)
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Trunk muscle activation at the initiation and braking of bilateral shoulder flexion movements of different amplitudes
- 2015
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if trunk muscle activation patterns during rapid bilateral shoulder flexions are affected by movement amplitude. Eleven healthy males performed shoulder flexion movements starting from a position with arms along sides (0°) to either 45°, 90° or 180°. EMG was measured bilaterally from transversus abdominis (TrA), obliquus internus (OI) with intra-muscular electrodes, and from rectus abdominis (RA), erector spinae (ES) and deltoideus with surface electrodes. 3D kinematics was recorded and inverse dynamics was used to calculate the reactive linear forces and torque about the shoulders and the linear and angular impulses. The sequencing of trunk muscle onsets at the initiation of arm movements was the same across movement amplitudes with ES as the first muscle activated, followed by TrA, RA and OI. All arm movements induced a flexion angular impulse about the shoulders during acceleration that was reversed during deceleration. Increased movement amplitude led to shortened onset latencies of the abdominal muscles and increased level of activation in TrA and ES. The activation magnitude of TrA was similar in acceleration and deceleration where the other muscles were specific to acceleration or deceleration. The findings show that arm movements need to be standardized when used as a method to evaluate trunk muscle activation patterns and that inclusion of the deceleration of the arms in the analysis allow the study of the relationship between trunk muscle activation and direction of perturbing torque during one and the same arm movement.
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| 15. |
- Ruiz, Jonatan R., et al.
(författare)
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Homocysteine levels in children and adolescents are associated with the methylenetetrahydrofolate reductase 677C>T genotype, but not with physical activity, fitness or fatness : the European Youth Heart Study
- 2007
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Ingår i: British Journal of Nutrition. - Cambridge : Cambridge university press. - 0007-1145 .- 1475-2662. ; 97:2, s. 255-262
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Tidskriftsartikel (refereegranskat)abstract
- To examine the associations of total plasma homocysteine (tHcy) with physical activity, cardiorespiratory fitness and fatness in children and adolescents, a cross-sectional study of 301 children (9–10 years old) and 379 adolescents (15–16 years old) was conducted. Physical activity was measured by accelerometry. Cardiorespiratory fitness was measured with a maximal ergometer bike test. Body fat was derived from the sum of five skinfold thicknesses. Genotyping for the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism was done by DNA sequencing. Fasting tHcy level was the outcome variable. Multiple regressions were used to determine the degree to which variance in tHcy was explained by physical activity, cardiorespiratory fitness and body fat, after controlling for potential confounders including MTHFR 677C>T genotype. tHcy levels were neither associated with any measure of level and pattern of physical activity nor with data on cardiorespiratory fitness, or body fat, in any age group after controlling for potential confounders including MTHFR 677C>T and even when subgroups 677TT and 677CC+CT were analysed separately. Mean values of tHcy were significantly higher in the TT subgroup compared with CC and CT subgroups in children (TT 7·4 μmol/l, CC 6·3 μmol/l, CT 6·6 μmol/l, P < 0·001 and P = 0·019, respectively) and adolescents (TT 16·9 μmol/l, CC 8·3 μmol/l, CT 9·0 μmol/l, both P < 0·001). The results suggest that physical activity, fitness and body fat are not associated with tHcy levels in children and adolescents, even after controlling for presence of the MTHFR 677C>T genotype, the main influence on tHcy levels in these subjects.
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| 16. |
- Liu, Yawei, et al.
(författare)
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Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE.
- 2006
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 12:5, s. 518-525
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Tidskriftsartikel (refereegranskat)abstract
- Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1–TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between neurons and T cells results in the conversion of encephalitogenic T cells to CD25+TGF-beta1+CTLA-4+FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4 but not TGF-beta1. Autocrine action of TGF-beta1, however, is important for the proliferative arrest of Treg cells. Blocking the B7 and TGF-beta pathways prevents the CNS-specific generation of Treg cells. These findings show that generation of neuron-dependent Treg cells in the CNS is instrumental in regulating CNS inflammation.
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| 17. |
- Lindberg, Frida A., et al.
(författare)
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SLC38A10 Deficiency in Mice Affects Plasma Levels of Threonine and Histidine in Males but Not in Females : A Preliminary Characterization Study of SLC38A10(-/-) Mice
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Solute carriers belong to the biggest group of transporters in the human genome, but more knowledge is needed to fully understand their function and possible role as therapeutic targets. SLC38A10, a poorly characterized solute carrier, is preliminary characterized here. By using a knockout mouse model, we studied the biological effects of SLC38A10 deficiency in vivo. We performed a transcriptomic analysis of the whole brain and found seven differentially expressed genes in SLC38A10-deficient mice (Gm48159, Nr4a1, Tuba1c, Lrrc56, mt-Tp, Hbb-bt and Snord116/9). By measuring amino acids in plasma, we found lower levels of threonine and histidine in knockout males, whereas no amino acid levels were affected in females, suggesting that SLC38A10(-/-) might affect sexes differently. Using RT-qPCR, we investigated the effect of SLC38A10 deficiency on mRNA expression of other SLC38 members, Mtor and Rps6kb1 in the brain, liver, lung, muscle, and kidney, but no differences were found. Relative telomere length measurement was also taken, as a marker for cellular age, but no differences were found between the genotypes. We conclude that SLC38A10 might be important for keeping amino acid homeostasis in plasma, at least in males, but no major effects were seen on transcriptomic expression or telomere length in the whole brain.
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| 18. |
- Andersson, Ingemar, 1950-
(författare)
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Långvarig smärta - en introduktion
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 387-400
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
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| 20. |
- Deshpande, J, et al.
(författare)
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Ultrastructural changes in the hippocampal CA1 region following transient cerebral ischemia: evidence against programmed cell death.
- 1992
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Ingår i: Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. - 0014-4819. ; 88:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- The ultrastructural changes in the pyramidal neurons of the CA1 region of the hippocampus were studied 6 h, 24 h, 48 h, and 72 h following a transient 10 min period of cerebral ischemia induced by common carotid occlusion combined with hypotension. The pyramidal neurons showed delayed neuronal death (DND), i.e. at 24 h and 48 h postischemia few structural alterations were noted in the light microscope, while at 72 h extensive neuronal degeneration was apparent. The most prominent early ultrastructural changes were polysome disaggregation, and the appearance of electron-dense fluffy dark material associated with tubular saccules. Mitochondria and nuclear elements appeared intact until frank neuronal degeneration. The dark material accumulated with extended periods of recirculation in soma and in the main trunks of proximal dendrites, often beneath the plasma membrane, less frequently in the distal dendrites and seldom in spines. Protein synthesis inhibitors (anisomycin, cycloheximide) and an RNA synthesis inhibitor (actinomycin D), administered by intrahippocampal injections or subcutaneously, did not mitigate neuronal damage. Therefore, DND is probably not apoptosis or a form of programmed cell death. We propose that the dark material accumulating in the postischemic period represents protein complexes, possibly aggregates of proteins or internalized plasma membrane fragments, which may disrupt vital cellular structure and functions, leading to cell death.
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| 21. |
- Lindberg, Frida A., et al.
(författare)
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SLC38A10 knockout mice display a decreased body weight and an increased risk-taking behavior in the open field test
- 2022
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media S.A.. - 1662-5153. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- The solute carrier 38 family (SLC38) is a family of 11 members. The most commonsubstrate among these are alanine and glutamine, and members are present in a widerange of tissues with important functions for several biological processes, such as liverand brain function. Some of these transporters are better characterized than others and,in this paper, a behavioral characterization of SLC38A10−/− mice was carried out. Abattery of tests for general activity, emotionality, motor function, and spatial memorywere used. Among these tests, the elevated plus maze, Y-maze, marble burying, andchallenging beamwalk have not been tested on the SLC38A10−/− mice previously, whilethe open field and the rotarod tests have been performed by the International MousePhenotyping Consortium (IMPC). Unlike the results from IMPC, the results from this studyshowed that SLC38A10−/− mice spend less time in the wall zone in the open field testthan WT mice, implying that SLC38A10-deficient mice have an increased explorativebehavior, which suggests an important function of SLC38A10 in brain. The present studyalso confirmed IMPC’s data regarding rotarod performance and weight, showing thatSLC38A10−/− mice do not have an affected motor coordination impairment and havea lower body weight than both SLC38A10+/− and SLC38A10+/+ mice. These resultsimply that a complete deficiency of the SLC38A10 protein might affect body weighthomeostasis, but the underlying mechanisms needs to be studied further.
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| 22. |
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| 23. |
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| 24. |
- Izsak, Julia, et al.
(författare)
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Differential acute impact of therapeutically effective and overdose concentrations of lithium on human neuronal single cell and network function
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Lithium salts are used as mood-balancing medication prescribed to patients suffering from neuropsychiatric disorders, such as bipolar disorder and major depressive disorder. Lithium salts cross the blood-brain barrier and reach the brain parenchyma within few hours after oral application, however, how lithium influences directly human neuronal function is unknown. We applied patch–clamp and microelectrode array technology on human induced pluripotent stem cell (iPSC)-derived cortical neurons acutely exposed to therapeutic (<1 mM) and overdose concentrations (>1 mM) of lithium chloride (LiCl) to assess how therapeutically effective and overdose concentrations of LiCl directly influence human neuronal electrophysiological function at the synapse, single-cell, and neuronal network level. We describe that human iPSC-cortical neurons exposed to lithium showed an increased neuronal activity under all tested concentrations. Furthermore, we reveal a lithium-induced, concentration-dependent, transition of regular synchronous neuronal network activity using therapeutically effective concentration (<1 mM LiCl) to epileptiform-like neuronal discharges using overdose concentration (>1 mM LiCl). The overdose concentration lithium-induced epileptiform-like activity was similar to the epileptiform-like activity caused by the GABAA-receptor antagonist. Patch–clamp recordings reveal that lithium reduces action potential threshold at all concentrations, however, only overdose concentration causes increased frequency of spontaneous AMPA-receptor mediated transmission. By applying the AMPA-receptor antagonist and anti-epileptic drug Perampanel, we demonstrate that Perampanel suppresses lithium-induced epileptiform-like activity in human cortical neurons. We provide insights in how therapeutically effective and overdose concentration of lithium directly influences human neuronal function at synapse, a single neuron, and neuronal network levels. Furthermore, we provide evidence that Perampanel suppresses pathological neuronal discharges caused by overdose concentrations of lithium in human neurons.
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