| 1. |
- af Bjerkén, Sara, et al.
(författare)
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Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures.
- 2007
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1133:1, s. 10-9
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Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and promotion of nerve fibers from midbrain dopamine neurons. It is also known to exert different effects on specific subpopulations of dopamine neurons. In organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth patterns, targeting the striatum differently. The aim of this study was to investigate the effect of GDNF on the formation of dopamine nerve fibers. Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice were studied. The results revealed that dopamine neurons survive in the absence of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and wildtype cultures, nerve fiber formation with two separate morphologies occurring either in the absence or the presence of astrocytes. The outgrowth that occurred in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve fibers guided by the presence of astrocytes were affected in that they reached significantly shorter distances from the gdnf gene-deleted tissue slice, compared to those measured in wildtype cultures. Treatment with GDNF reversed this effect and increased nerve fiber density independent of genotype. Furthermore, migration of astrocytes reached significantly shorter distances from the tissue slice in GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve fiber formation - possibly as an indirect effect of astrocytic stimulation.
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| 2. |
- Granholm, Ann-Charlotte E, et al.
(författare)
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Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings
- 2024
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 147, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.
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| 3. |
- Hamlett, Eric D., et al.
(författare)
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Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome
- 2017
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Ingår i: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 13:5, s. 541-549
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Individuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-β (Aβ) peptides and phosphorylated-tau in neuronal exosomes may document preclinical AD.METHODS: AD neuropathogenic proteins Aβ1-42, P-T181-tau, and P-S396-tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls.RESULTS: Neuronal exosome levels of Aβ1-42, P-T181-tau, and P-S396-tau were significantly elevated in individuals with DS compared with age-matched controls at all ages beginning in childhood. No significant gender differences were observed.DISCUSSION: These early increases in Aβ1-42, P-T181-tau, and P-S396-tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.
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| 4. |
- Håkansson, Krister, 1952-, et al.
(författare)
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BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness : Associations with Working Memory Function
- 2017
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 55:2, s. 645-657
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) has a central role in brain plasticity by mediating changes in cortical thickness and synaptic density in response to physical activity and environmental enrichment. Previous studies suggest that physical exercise can augment BDNF levels, both in serum and the brain, but no other study has examined how different types of activities compare with physical exercise in their ability to affect BDNF levels. By using a balanced cross over experimental design, we exposed nineteen healthy older adults to 35-minute sessions of physical exercise, cognitive training, and mindfulness practice, and compared the resulting changes in mature BDNF levels between the three activities. We show that a single bout of physical exercise has significantly larger impact on serum BDNF levels than either cognitive training or mindfulness practice in the same persons. This is the first study on immediate BDNF effects of physical activity in older healthy humans and also the first study to demonstrate an association between serum BDNF responsivity to acute physical exercise and working memory function. We conclude that the BDNF increase we found after physical exercise more probably has a peripheral than a central origin, but that the association between post-intervention BDNF levels and cognitive function could have implications for BDNF responsivity in serum as a potential marker of cognitive health.
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| 5. |
- Ledreux, Aurelie, et al.
(författare)
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Differential Effects of Physical Exercise, Cognitive Training, and Mindfulness Practice on Serum BDNF Levels in Healthy Older Adults : A Randomized Controlled Intervention Study
- 2019
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 71:4, s. 1245-1261
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that an active lifestyle is associated with better brain health and a longer life, compared to a more sedentary lifestyle. These studies, both on human and animal subjects, have typically focused on a single activity, usually physical exercise, but other activities have received an increasing interest. One proposed mechanism is that physical exercise increases levels of brain-derived neurotrophic factor (BDNF) in the brain. For the first time, the long-term effects on serum BDNF levels were compared in persons who engaged in either physical exercise training, cognitive training, or mindfulness practice during 5 weeks, and compared with an active control group. Two cohorts of healthy older individuals, one from the Boston area in the US and one from the Vaxjo area in Sweden, participated. A total of 146 participants were randomly assigned to one of the four groups. All interventions were structurally similar, using interactive, computer-based software that directed participants to carry out specified activities for 35 minutes/day, 5 days per week for 5 weeks. Blood samples were obtained at baseline and soon after the completion of the 5-week long intervention program, and serum BDNF levels were measured using a commercially available ELISA. Only the group that underwent cognitive training increased their serum BDNF levels after 5 weeks of training (F-1,F-74 = 4.22, p = 0.044, partial eta(2) = 0.054), corresponding to an average 10% increase. These results strongly suggest that cognitive training can exert beneficial effects on brain health in an older adult population.
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| 6. |
- Nicastri, Casey M., et al.
(författare)
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BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults
- 2022
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The often-cited mechanism linking brain-derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF. Methods A total of 144 heathy older adults completed a 5-week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre- and post-intervention. Results Linear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention-related improvement in task performance. Regression analyses showed that, across all intervention conditions, increased BDNF levels were associated with increased DST scores. Discussion This study appears to be the first to suggest that BDNF helps mediate improvements in cognition after working memory training in healthy older adults. Highlights Older adults were randomized to physical activity, mindfulness, cognitive training (computerized cognitive training (CCT), or control. CCT, but no other condition, led to increased serum brain-derived neurotrophic factor (BDNF) levels. CCT led to improvement on the untrained Digit Symbol Test (DST) of speed/working memory. Path analysis: increases in BDNF mediate intervention-related improvement on DST. Increases in BDNF associated with improved DST across all experimental groups.
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