| 1. |
- Anderberg, Rozita H, 1976, et al.
(author)
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Treatment with RNase alleviates brain injury but not neuroinflammation in neonatal hypoxia/ischemia
- 2024
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In: JOURNAL OF NEUROSCIENCE RESEARCH. - 0360-4012 .- 1097-4547. ; 102:4
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Journal article (peer-reviewed)abstract
- There is a need for new treatments to reduce brain injuries derived from neonatal hypoxia/ischemia. The only viable option used in the clinic today in infants born at term is therapeutic hypothermia, which has a limited efficacy. Treatments with exogenous RNase have shown great promise in a range of different adult animal models including stroke, ischemia/reperfusion injury, or experimental heart transplantation, often by conferring vascular protective and anti-inflammatory effects. However, any neuroprotective function of RNase treatment in the neonate remains unknown. Using a well-established model of neonatal hypoxic/ischemic brain injury, we evaluated the influence of RNase treatment on RNase activity, gray and white matter tissue loss, blood-brain barrier function, as well as levels and expression of inflammatory cytokines in the brain up to 6 h after the injury using multiplex immunoassay and RT-PCR. Intraperitoneal treatment with RNase increased RNase activity in both plasma and cerebropinal fluids. The RNase treatment resulted in a reduction of brain tissue loss but did not affect the blood-brain barrier function and had only a minor modulatory effect on the inflammatory response. It is concluded that RNase treatment may be promising as a neuroprotective regimen, whereas the mechanistic effects of this treatment appear to be different in the neonate compared to the adult and need further investigation.
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| 2. |
- Andin, Josefine, 1979-, et al.
(author)
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Arithmetic in the adult deaf signing brain
- 2020
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In: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 98:4, s. 643-654
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Journal article (peer-reviewed)abstract
- We have previously shown that deaf signers recruit partially different brain regions during simple arithmetic compared to a group of hearing non-signers, despite similar performance. Specifically, hearing individuals show more widespread activation in brain areas that have been related to the verbal system of numerical processing, i.e., the left angular and inferior frontal gyrus, whereas deaf individuals engaged brain areas that have been related to the quantity system of numerical processing, i.e., the right horizontal intraparietal sulcus. This indicates that compared to hearing non-signers, deaf signers can successfully make use of processes located in partially different brain areas during simple arithmetic. In this study, which is a conceptual replication and extension of the above-presented study, the main aim is to understand similarities and differences in neural correlates supporting arithmetic in deaf compared to hearing individuals. The primary objective is to investigate the role of the right horizontal intraparietal gyrus, the left inferior frontal gyrus, the hippocampus, and the left angular gyrus during simple and difficult arithmetic and how these regions are connected to each other. A second objective is to explore what other brain regions support arithmetic in deaf signers. Up to 34 adult deaf signers and the same amount of hearing non-signers will be enrolled in an functional magnetic resonance imaging study that will include simple and difficult subtraction and multiplication. Brain imaging data will be analyzed using whole-brain analysis, region of interest analysis and connectivity analysis. This is the first study to investigate neural underpinnings of arithmetic of different difficulties in deaf individuals.
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| 3. |
- Andin, Josefine, 1979-, et al.
(author)
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Arithmetic in the signing brain : Differences and similarities in arithmetic processing between deaf signers and hearing non-signers
- 2023
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In: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 101:1, s. 172-195
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Journal article (peer-reviewed)abstract
- Deaf signers and hearing non-signers have previously been shown to recruit partially different brain regions during simple arithmetic. In light of the triple code model, the differences were interpreted as relating to stronger recruitment of the verbal system of numerical processing, that is, left angular and inferior frontal gyrus, in hearing non-signers, and of the quantity system of numerical processing, that is, right horizontal intraparietal sulcus, for deaf signers. The main aim of the present study was to better understand similarities and differences in the neural correlates supporting arithmetic in deaf compared to hearing individuals. Twenty-nine adult deaf signers and 29 hearing non-signers were enrolled in an functional magnetic resonance imaging study of simple and difficult subtraction and multiplication. Brain imaging data were analyzed using whole-brain analysis, region of interest analysis, and functional connectivity analysis. Although the groups were matched on age, gender, and nonverbal intelligence, the deaf group performed generally poorer than the hearing group in arithmetic. Nevertheless, we found generally similar networks to be involved for both groups, the only exception being the involvement of the left inferior frontal gyrus. This region was activated significantly stronger for the hearing compared to the deaf group but showed stronger functional connectivity with the left superior temporal gyrus in the deaf, compared to the hearing, group. These results lend no support to increased recruitment of the quantity system in deaf signers. Perhaps the reason for performance differences is to be found in other brain regions not included in the original triple code model.
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| 4. |
- Behere, Anish, 1993-, et al.
(author)
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Visualization of early oligomeric α‐synuclein pathology and its impact on the dopaminergic system in the (Thy‐1)‐h[A30P]α‐syn transgenic mouse model
- 2021
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In: Journal of Neuroscience Research. - : John Wiley & Sons. - 0360-4012 .- 1097-4547. ; 99:10, s. 2525-2539
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Journal article (peer-reviewed)abstract
- Aggregation of alpha-synuclein (alpha-syn) into Lewy bodies and Lewy neurites is a pathological hallmark in the Parkinson ' s disease (PD) brain. The formation of alpha-syn oligomers is believed to be an early pathogenic event and the A30P mutation in the gene encoding alpha-syn, causing familial PD, has been shown to cause an accelerated oligomerization. Due to the problem of preserving antigen conformation on tissue surfaces, alpha-syn oligomers are difficult to detect ex vivo using conventional immunohistochemistry with oligomer-selective antibodies. Herein, we have instead employed the previously reported alpha-syn oligomer proximity ligation assay (ASO-PLA), along with a wide variety of biochemical assays, to discern the pathological progression of alpha-syn oligomers and their impact on the dopaminergic system in male and female (Thy-1)-h[A30P]alpha-syn transgenic (A30P-tg) mice. Our results reveal a previously undetected abundance of alpha-syn oligomers in midbrain of young mice, whereas phosphorylated (pS129) and proteinase k-resistant alpha-syn species were observed to a larger extent in aged mice. Although we did not detect loss of dopaminergic neurons in A30P-tg mice, a dysregulation in the monoaminergic system was recorded in older mice. Taken together, ASO-PLA should be a useful method for the detection of early changes in alpha-syn aggregation on brain tissue, from experimental mouse models in addition to post mortem PD cases.
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| 5. |
- Bränn, Emma, et al.
(author)
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Inflammatory markers in women with postpartum depressive symptoms
- 2020
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In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 98:7, s. 1309-1321
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Journal article (peer-reviewed)abstract
- Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.
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| 6. |
- Eide, P. K., et al.
(author)
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Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension
- 2021
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In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 99:2, s. 467-480
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Journal article (peer-reviewed)abstract
- Idiopathic intracranial hypertension (IIH) primarily affects fertile, overweight women, and presents with the symptoms of raised intracranial pressure. The etiology is unknown but has been thought to relate to cerebrospinal fluid disturbance or cerebral venous stenosis. We have previously found evidence that IIH is also a disease of the brain parenchyma, evidenced by alterations at the neurogliovascular interface, including astrogliosis, pathological changes in the basement membrane and pericytes, and alterations of perivascular aquaporin-4. The aim of this present electron microscopic study was to examine whether mitochondria phenotype was changed in IIH, particularly focusing on perivascular astrocytic endfeet and neurons (soma and pre- and postsynaptic terminals). Cortical brain biopsies of nine reference individuals and eight IIH patients were analyzed for subcellular distribution and phenotypical features of mitochondria using transmission electron microscopy. We found significantly increased prevalence of pathological mitochondria and reduced number of normal mitochondria in astrocytic endfeet of IIH patients. The degree of astrogliosis correlated negatively with the number of normal mitochondria in astrocytic endfoot processes. Moreover, we found significantly increased number of pathological mitochondria in pre- and postsynaptic neuronal terminals, as well as significantly shortened distance between mitochondria and endoplasmic reticulum contacts. Finally, the length of postsynaptic density, a marker of synaptic strength, was on average reduced in IIH. The present data provide evidence of pathological mitochondria in perivascular astrocytes endfeet and neurons of IIH patients, highlighting that impaired metabolism at the neurogliovascular interface may be a facet of IIH. © 2020 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC
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| 8. |
- Jonasson, My, et al.
(author)
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Quantification of aromatase binding in the female human brain using [11 C]cetrozole positron emission tomography.
- 2020
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In: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 98:11, s. 2208-2218
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Journal article (peer-reviewed)abstract
- Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11 C]cetrozole. Anatomical magnetic resonance and 90-min dynamic [11 C]cetrozole PET-CT scans were performed on healthy women. Volume of interest (VOI)-based analyses with a plasma-input function were performed using the single-tissue and two-tissue (2TCM) reversible compartment models and plasma-input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI-based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma-input- and reference tissue-based methods and comparisons between scan durations were assessed by linear regression. The [11 C]cetrozole time-activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND ), with cerebellum as reference region, can be used to estimate [11 C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11 C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue-based approach.
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