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| 2. |
- Aklillu, Eleni, et al.
(författare)
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Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression.
- 2009
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 19:4, s. 267-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Monoamine oxidase-A (MAO-A) is a key mitochondrial enzyme that metabolizes biogenic amine neurotransmitters such as dopamine and serotonin. Individuals with atypical depression (AD) are particularly responsive to treatment with MAO inhibitors (MAOIs). Biomarker tests are essential for prompt diagnosis of AD, and to identify those with an altered brain neurotransmitter metabolism who may selectively respond to MAOI therapy. METHODS: In a sample of 118 Scandinavian patients with treatment-resistant depression who are naive to MAOI therapy, we investigated the associations between a common MAOA functional promoter polymorphism (MAOA-uVNTR), cerebrospinal fluid (CSF) neurotransmitter metabolites, and AD susceptibility. The metabolites for dopamine (homovanillic acid, HVA), serotonin (5-hydroxyindoleacetic acid) and noradrenaline (3-methoxy-4-hydroxyphenylglycol) were measured in the CSF. RESULTS: AD was associated with the female sex and a higher HVA in CSF (P=0.008). The carriers of the MAOA-uVNTR short allele were significantly overrepresented among women with AD (P=0.005; odds ratio=4.76; 95% confidence interval=1.5-13.1; statistical power=80.0%). Moreover, the MAOA-uVNTR genotype significantly influenced the HVA concentration (P=0.01) and showed a strong trend in relation to 5-hydroxyindoleacetic acid concentration (P=0.057) in women. The mediational statistical analyses showed the CSF-HVA concentration as a key driver of the relationship between MAOA-uVNTR genotype and AD. CONCLUSION: The association of the MAOA-uVNTR with both susceptibility to AD and dopamine metabolite (HVA) concentration lends further biological plausibility for high MAO-A enzyme activity as a mechanistic factor for genetic predisposition to AD through altered dopamine turnover. Our observations provide new evidence on the in-vivo functional significance of the MAOA-uVNTR short allele as a high activity variant.
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| 3. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
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Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications.
- 2010
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Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:7, s. 2161-82
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Tidskriftsartikel (refereegranskat)abstract
- Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-gamma treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.
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| 5. |
- Hanson, Ellen, et al.
(författare)
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No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes
- 2012
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 130:3, s. 339-342
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke. Materials and methods: The study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70 years, and 600 matched controls. Patients were classified according to the TOAST criteria. Results: There was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype. Conclusions: The findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.
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| 6. |
- Hellman, Urban, 1966-, et al.
(författare)
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Presence of hyaluronan in lung alveoli in severe Covid-19 : an opening for new treatment options?
- 2020
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:45, s. 15418-15422
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Tidskriftsartikel (refereegranskat)abstract
- Severe corona virus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined.The aim of the study was to demonstrate if the lungs of fatal Covid-19 contain hyaluronan as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly.Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue.Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up for new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.
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| 7. |
- Karlsson, Sara, 1980, et al.
(författare)
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Effects of sex and gonadectomy on social investigation and social recognition in mice
- 2015
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Ingår i: Bmc Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: An individual's ability to recognise and pay attention to others is crucial in order to behave appropriately in various social situations. Studies in humans have shown a sex bias in sociability as well as social memory, indicating that females have better face memory and gaze more at the eyes of others, but information about the factors that underpin these differences is sparse. Our aim was therefore to investigate if sociability and social recognition differ between female and male mice, and if so, to what extent gonadal hormones may be involved. Intact and gona-dectomised male and female mice were assessed for sociability and social recognition using the three-chambered sociability paradigm, as well as the social discrimination test. Furthermore, we conducted a novel object recognition test, a locomotor activity test and an odour habituation/dishabituation test. Results: The present study showed that the ability to recognise other individuals is intact in males with and without gonads, as well as in intact females, whereas it is hampered in gonadectomised females. Additionally, intact male mice displayed more persistent investigatory behaviour compared to the other groups, although the intact females showed elevated basal locomotor activity. In addition, all groups had intact object memory and habituated to odours. Conclusions: Our results suggest that intact male mice investigate conspecifics more than females do, and these differences seem to depend upon circulating hormones released from the testis. As these results seem to contrast what is known from human studies, they should be taken into consideration when using the three-chambered apparatus, and similar paradigms as animal models of social deficits in e.g. autism. Other behavioural tests, and animal models, may be more suitable for translational studies between patients and experimental animals.
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| 8. |
- Karlsson, Sara, 1980, et al.
(författare)
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Neural Androgen Receptors Modulate Gene Expression and Social Recognition But Not Social Investigation
- 2016
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The role of sex and androgen receptors (ARs) for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest toward male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDel males recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esrl, Cyp19a1, Ucn3, Crh. and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation toward both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William's syndrome.
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| 9. |
- Karlsson, Sara, 1980
(författare)
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Sex steroids and social behavior: from mouse to human
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Social behavior is a classification of various behaviors such as sexual behavior, aggressive behavior, social memory and sociability. These behaviors are under the regulation of the brain, and the sex steroids influence important brain regions that control these behaviors in both humans and other animals. To behave and respond adequately in social situations is crucial for interacting with others in an appropriate way. Several disorders, e.g. autism spectrum disorders (ASD), display deficits in social abilities and, interestingly, show differences between females and males in prevalence and symptoms. Moreover, testosterone is hypothesized to be one of the causative factors behind the etiology of ASD. Both the androgen and estrogen receptors are of known importance for sexually dimorphic social behaviors such as sexual and aggressive behaviors. Furthermore, estrogen receptors are essential for social memory in rodents, and human studies show a female bias towards better social memory. Less is known about the role of androgen receptors. The aims of this thesis were to elucidate if sex, sex steroids and the androgen receptor are involved in social memory and sociability in mice, if genes and proteins in brain regions regulated by sex steroids, with known importance for social behavior, show sexual dimorphisms or are regulated by androgen receptors, and if genetic variations in sex steroid-related genes are involved in social memory and/or autistic-like traits in human. The results show that a) testosterone is not crucial for social memory or sociability but for the persistence of social investigation, b) estrogen is importance for social memory but not for sociability, c) only when the conspecifics were male did the androgen receptor appear to be involved in social memory, d) a small number of genes involved in sex steroid synthesis, were regulated by the androgen receptor but e.g. the oxytocin receptor show androgen receptor dependant sexual dimorphic expression, e) proteins expressed in postnatal day 8 old mice did not show great differences between the sexes, or between males with or without the androgen receptor, f) genetic variations in the estrogen receptors were associated with better social memory in women, and g) genetic variations in the transport protein of sex steroids were associated with language disabilities, specifically in boys. The main findings presented in this thesis are thus that sex steroids are implicated in different manners in sociability and social memory in mice, and that genetic variation in sex steroid-related genes are associated with social abilities in humans.
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| 10. |
- Karlsson, Sara, 1980, et al.
(författare)
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Social memory associated with estrogen receptor polymorphisms in women
- 2016
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5016 .- 1749-5024. ; 11:6, s. 877-883
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR. Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice.
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