| 1. |
- Hellsten, Johan, et al.
(författare)
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Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment
- 2002
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 16:2, s. 283-290
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Tidskriftsartikel (refereegranskat)abstract
- Major depression is often associated with elevated glucocorticoid levels. High levels of glucocorticoids reduce neurogenesis in the adult rat hippocampus. Electroconvulsive seizures (ECS) can enhance neurogenesis, and we investigated the effects of ECS in rats where glucocorticoid levels were elevated in order to mimic conditions seen in depression. Rats given injections of corticosterone or vehicle for 21 days were at the end of this period treated with either a single or five daily ECSs. Proliferating cells were labelled with bromodeoxyuridine (BrdU). After 3 weeks, BrdU-positive cells in the dentate gyrus were quantified and analyzed for co-labelling with the neuronal marker neuron-specific nuclear protein (NeuN). In corticosterone-treated rats, neurogenesis was decreased by 75%. This was counteracted by a single ECS. Multiple ECS further increased neurogenesis and no significant differences in BrdU/NeuN positive cells were detected between corticosterone- and vehicle-treated rats given five ECS. Approximately 80% of the cells within the granule cell layer and 10% of the hilar cells were double-labelled with BrdU and NeuN. We therefore conclude that electroconvulsive seizures can increase hippocampal neurogenesis even in the presence of elevated levels of glucocorticoids. This further supports the hypothesis that induction of neurogenesis is an important event in the action of antidepressant treatment.
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| 2. |
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| 3. |
- Bangsbo, Jens, et al.
(författare)
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Copenhagen Consensus statement 2019 : physical activity and ageing
- 2019
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Ingår i: British Journal of Sports Medicine. - London : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 53:14, s. 856-858
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Tidskriftsartikel (refereegranskat)abstract
- From 19th to 22nd November 2018, 26 researchers representing nine countries and a variety of academic disciplines met in Snekkersten, Denmark, to reach evidence-based consensus about physical activity and older adults. It was recognised that the term ‘older adults’ represents a highly heterogeneous population. It encompasses those that remain highly active and healthy throughout the life-course with a high intrinsic capacity to the very old and frail with low intrinsic capacity. The consensus is drawn from a wide range of research methodologies within epidemiology, medicine, physiology, neuroscience, psychology and sociology, recognising the strength and limitations of each of the methods. Much of the evidence presented in the statements is based on longitudinal associations from observational and randomised controlled intervention studies, as well as quantitative and qualitative social studies in relatively healthy community-dwelling older adults. Nevertheless, we also considered research with frail older adults and those with age-associated neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease, and in a few cases molecular and cellular outcome measures from animal studies. The consensus statements distinguish between physical activity and exercise. Physical activity is used as an umbrella term that includes both structured and unstructured forms of leisure, transport, domestic and work-related activities. Physical activity entails body movement that increases energy expenditure relative to rest, and is often characterised in terms of intensity from light, to moderate to vigorous. Exercise is defined as a subset of structured physical activities that are more specifically designed to improve cardiorespiratory fitness, cognitive function, flexibility balance, strength and/or power. This statement presents the consensus on the effects of physical activity on older adults’ fitness, health, cognitive functioning, functional capacity, engagement, motivation, psychological well-being and social inclusion. It also covers the consensus on physical activity implementation strategies. While it is recognised that adverse events can occur during exercise, the risk can be minimised by carefully choosing the type of activity undertaken and by consultation with the individual’s physician when warranted, for example, when the individual is frail, has a number of co-morbidities, or has exercise-related symptoms, such as chest pain, heart arrhythmia or dizziness. The consensus was obtained through an iterative process that began with the presentation of the state-of-the-science in each domain, followed by group and plenary discussions. Ultimately, the participants reached agreement on the 30-item consensus statements.
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| 4. |
- Ekstrand, Joakim, et al.
(författare)
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Differential inhibition of neurogenesis and angiogenesis by corticosterone in rats stimulated with electroconvulsive seizures
- 2008
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Ingår i: Progress in Neuro-Psychopharmacology and Biological Psychiatry. - : Elsevier BV. - 0278-5846. ; 32:6, s. 1466-1472
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Forskningsöversikt (refereegranskat)abstract
- Antidepressant drugs and electroconvulsive seizure (ECS)-treatment, an animal model of electroconvulsive therapy, induce neurogenesis in adult rats. Stress and high levels of corticosterone (CORT) on the contrary inhibit neurogenesis. Hippocampal neurogenesis has been described to occur in an angiogenic niche where proliferation of neural progenitors takes place in an environment with active vascular growth. Here we investigate the effect of ECS-treatment on the proliferation of endothelial cells and neuronal precursors in hippocampus of CORT-treated rats. Bromodeoxyuridine (BrdU) was used to identify dividing cells. The number of newborn neuronal precursors and endothelial cells was quantified in the subgranular zone (SGZ) and the molecular layer (ML) of the dentate gyrus. The increase in neuronal precursor proliferation in the SGZ following ECS-treatment was not inhibited by elevated levels of CORT despite CORT strongly inhibiting ECS-induced endothelial cell proliferation. Also in the ML CORT-treatment inhibited the ECS-induced angiogenic response. We conclude that despite common factors regulating neurogenesis and angiogenesis, ECS-induced proliferation of neuronal precursors can take place even if the angiogenic response is blunted. Whether inhibition of angiogenesis affects other steps in the chain of events leading to the formation of fully integrated granule neurons remains to be elucidated. (C) 2008 Elsevier Inc. All rights reserved.
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| 5. |
- Ekstrand, Joakim, et al.
(författare)
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Environmental enrichment, exercise and corticosterone affect endothelial cell proliferation in adult rat hippocampus and prefrontal cortex.
- 2008
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 442, s. 203-207
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Tidskriftsartikel (refereegranskat)abstract
- Stress and environmental enrichment have opposing effects on cerebral cellular plasticity. Stress-induced disturbances in neuronal and glial plasticity have been implicated in the pathophysiology of affective disorders. Patients with depression often show volume reductions in specific brain regions. The mechanisms behind these changes are not well understood, but animal studies have indicated that increased levels of glucocorticoids and stress have negative impact on the neuronal and glial cell populations. On the contrary, enriched environment and physical activity have positive effects. In this study we have examined the effect of corticosterone (CORT), environmental enrichment (EE) and running on angiogenesis in hippocampus and prefrontal cortex (PFC). We demonstrate a dramatic inhibition in endothelial cell proliferation in these brain regions in CORT-treated rats. Environmental enrichment had the opposite effect and stimulated endothelial cell proliferation both in the hippocampus and in the PFC. Running had a stimulatory effect in hippocampus, but not in the PFC. We suggest that the angiostatic effect of CORT demonstrated in this study might be paralleled in human subjects exposed to high levels of stress hormones for prolonged periods of time. Raised cortisol levels in depressed or old patients could, by reducing endothelial cell formation/turnover, lead to rarefaction and aging of the vascular bed, and as a result, neuronal function could be impaired. It is tempting to speculate that a physically and intellectually active life may protect against stress-induced vascular changes. Therapeutic agents also targeting the cerebral vasculature could consequently constitute a new tool in the combat of stress-related disorders.
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| 6. |
- Fredriksson, Robert, et al.
(författare)
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The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.
- 2019
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 15:12
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Tidskriftsartikel (refereegranskat)abstract
- SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.
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| 7. |
- Fröbert, Ole, et al.
(författare)
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Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction
- 2013
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 369:17, s. 1587-1597
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. MethodsWe conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. ResultsNo patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. ConclusionsRoutine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.)
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| 8. |
- Hellsten, Johan, et al.
(författare)
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Electroconvulsive seizures induce angiogenesis in adult rat hippocampus
- 2005
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 58:11, s. 871-878
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Tidskriftsartikel (refereegranskat)abstract
- Background: Electroconvulsive seizure (ECS)-treatment, a model for electroconvulsive therapy (ECT) has been shown to induce proliferation of endothelial cells in the dentate gyrus (DG) of adult rats. Here we quantified the net angiogenic response after hypoxia a known inducer of aniogenesis. Therefore we also examined the effect of oxygenation on ECS-induced proliferation of endothelial cells. Methods: Total endothelial cell numbers and vessel length were estimated utilizing design based stereological analysis methods. Endothelial cell proliferation in the DG after ECS with or withouy oxygenation was assessed using bromodeoxyuridine. Results: The total number of endothelial cell numbers and vessels lenght was increased. Oxygenation did not abolish the ECS-induced proliferation of endothelial cells in the DG. Conclusions: ECS-treatment induces a dramatic increase in endothelial cell proliferation leading to a 30% increase in the total numberof endothelial cells. The increase in cell number resulted i na 16% increase in vessel length. These findings raise the possibility that similar vascular growth is induced by clinically administered ECT.
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| 9. |
- Hellsten, Johan
(författare)
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Neurogenic and angiogenic actions of electroconvulsive seizures in adult rat brain
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the current thesis, the neurogenic and angiogenic response to electroconvulsive seizure (ECS)-treatment was investigated in the adult rat brain. ECS-treatment is an animal model for the antidepressant treatment electroconvulsive therapy (ECT), which is considered to be the most effective antidepressant treatment modality today, however with not yet fully understood modes of action. Depression, which is a common and devastating illness has recently been proposed to be caused by a decreased hippocampal neurogenesis and cellular plasticity in general, possibly due to elevated levels of the stress hormone cortisol, manifesting itself as a reduction in hippocampal volume. In the current thesis, ECS-treatment was shown to be able to oppose stress hormone-induced decrease in hippocampal neurogenesis and also induce proliferation of non-neuronal cells. A large majority of these cells were identified as being endothelial cells, and neurogenesis and angiogenesis in response to ECS-treatment seemingly occurred in concert. In addition to neurogenesis, ECS-treatment induced strong neuronal activation in the hypothalamus, co-localising with a strong angiogenic response. Endothelial cells have been shown to influence neuronal and glial function and we hypothesise that the increase in hypothalamic endothelial cell proliferation could for example influence neuroendocrine signaling. Besides possibly influencing neuronal and glial function, endothelial cells are building blocks of blood vessels. We detect a strong angiogenic response in the hippocampus, which in fact results in a 16% increase in vessel length in the molecular layer of the dentate gyrus. This finding has important implications for the trophic actions of ECS-treatment. In addition to counteracting decreases in neurogenesis, ECS-treatment increase the vascularization of a structure that has been shown to be vulnerable to stress and decrease in size in depressed patients. Understanding this angiogenic response and possibly being able to stimulate it by other means than ECS-treatment could possibly lead to the development of new and more effective antidepressant treatments.
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| 10. |
- Jahnson, Staffan, et al.
(författare)
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Urinary diversion after cystectomy for bladder cancer: A population-based study in Sweden
- 2010
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Ingår i: SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 44:2, s. 69-75
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. Material and methods. Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). Results. During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p andlt; 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p andlt; 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p andlt; 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). Conclusions. Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.
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