oru.sePublications
Change search
Refine search result
1 - 16 of 16
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Comasco, Erika
    et al.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Vumma, Ravi
    Department of Chemistry and Biomedical Sciences, Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden.
    Toffoletto, R.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Johansson, Jessica
    Örebro University, School of Health Sciences. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Flyckt, Lena
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
    Lewander, Tommy
    Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Oreland, Lars
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Bjerkenstedt, Lars
    Strömstad Academy, Strömstad, Sweden.
    Andreou, Dimitrios
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
    Söderman, Erik
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
    Terenius, Lars
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden.
    Agartz, Ingrid
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden; NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway .
    Jönsson, Erik G.
    Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden; NORMENT, K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Venizelos, Nikolaos
    Örebro University, School of Health Sciences.
    Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia2017In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 74, no 2, p. 96-103Article in journal (Refereed)
    Abstract [en]

    Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

  • 2.
    Engwall, Magnus
    et al.
    Örebro University, School of Science and Technology.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Westman, Ola
    Örebro University, School of Science and Technology.
    Larsson, Maria
    Örebro University, School of Science and Technology.
    Nordén, Marcus
    Örebro University, School of Science and Technology.
    Hollert, Henner
    Rheinisch-Westfälische Technische Hochschule (RWTH), Aachen, Germany.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Polycyclic aromatic hydrocarbons (PAHs) reduce hepatic beta-oxidation of fatty acids in chick embryos2013In: Environmental science and pollution research international, ISSN 0944-1344, E-ISSN 1614-7499, Vol. 20, no 3, p. 1881-1888Article in journal (Refereed)
    Abstract [en]

    Polycyclic aromatic hydrocarbons (PAHs) are widespread fused-ring contaminants formed during incomplete combustion of almost all kind of organic materials from both natural and anthropogenic sources. Some PAHs have been shown to be carcinogenic to humans, and a wide range of PAHs are found in wildlife all around the globe including avian species. The purpose of this project was to assess the effects of a standard mixture of 16 PAHs (United States Environmental Protection Agency) on the hepatic fatty acid beta-oxidation in chicken embryos (Gallus gallus domesticus) exposed in ovo. The hepatic beta-oxidation was measured using a tritium release assay with [9,10-H-3]-palmitic acid (16:0) as substrate. Treated groups were divided into groups of 0.05, 0.1, 0.3, 0.5, and 0.8 mg PAHs/kg egg weight. The hepatic beta-oxidation was reduced after exposure in ovo to the 16 PAHs mixture compared to control. The mechanisms causing reduced fatty acid oxidation in the present study are unclear, however may be due to deficient membrane structure, the functionality of enzymes controlling the rate of fatty acid entering into the mitochondria, or complex pathways connected to endocrine disruption. To the best of our knowledge, this is the first time a PAH-caused reduction of hepatic beta-oxidation of fatty acids in avian embryos has been observed. The implication of this finding on risk assessment of PAH exposure in avian wildlife remains to be determined.

  • 3.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences.
    Amino acid transport and receptor binding properties in neuropsychiatric disorders using the fibroblast cell model2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Altered transport of the catecholamines and serotonin precursor amino acids tyrosine and tryptophan, might be one explanation for the dysfunctional neurotransmission implicated in the pathophysiology of bipolar disorder and Attention Deficit/Hyperactivity Disorder (ADHD). In previous studies, an altered amino acid transport has been found in schizophrenia and autism, when using the fibroblast cell model. The aim of this thesis was to investigate if the transport of precursor amino acids also may be altered in bipolar disorder and ADHD, and to relate the pre-synaptic activity (transport) with post-synaptic activity (receptors). A functional characterization of tryptophan transport in fibroblasts was also motivated, since the transport of tryptophan in fibroblast cells has not been fully explored.

    Fibroblast cell lines from patients with bipolar type-1 disorder, from children with ADHD and from controls were included in the studies. The maximal transport capacity (Vmax) and affinity constant (Km) of tyrosine, tryptophan and alanine transport in bipolar patients and ADHD children were determined. Tryptophan transport characterization included; 1) measuring the uptake of tryptophan at high and low concentrations in the presence or absence of transporter selective inhibitors; 2) determination of Vmax and Km of tryptophan transport at high and low concentrations; 3) sodium dependency studies of tryptophan uptake. All transport studies were done using the cluster tray method. Furthermore, the maximal binding capacity (Bmax) and the equilibrium dissociation constant (KD) of muscarinic acetylcholine receptors (mAChRs) were determined in the ADHD children by a radioligand binding assay, using the mAChRs antagonist QNB.

    In patients with bipolar disorder a decreased Vmax in the transport of tyrosine was observed (p=0.027), while the children with ADHD had a decreased Vmax of tryptophan transport (p=0.039) and an increased Vmax of alanine transport (p=0.031). Children with a hereditary ADHD also had a significantly decreased Bmax (p=0.01). The uptake of tryptophan at both high and low concentrations was partly sodium dependent and the inhibitors had different inhibitory effects on the tryptophan uptake. The uptake of tryptophan at high concentration had low affinity and high Vmax, whilst at low concentration the transport was with high affinity and low Vmax.

    Altered amino acid transport was observed in fibroblasts of both bipolar disorder patients and ADHD children, which might indicate that the availability of precursor amino acid in the brain is altered. This could lead to disturbances, directly or indirectly, in the catecholaminergic and serotonergic systems. Children with hereditary ADHD might also have reduced levels of mAChRs in the CNS that could indirectly affect the dopaminergic activity. The uptake of tryptophan was through multiple transporters and was different at different substrate concentrations in terms of sodium dependency, affects of inhibitors and kinetic parameters.

    List of papers
    1. Aberrant amino acid transport in fibroblasts from patients with bipolar disorder
    Open this publication in new window or tab >>Aberrant amino acid transport in fibroblasts from patients with bipolar disorder
    Show others...
    2009 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 457, no 1, p. 49-52Article in journal (Refereed) Published
    Abstract [en]

    Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n = 10) and healthy controls (n = 10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (Vmax) and affinity constant (Km) were determined. A significantly lower Vmax for tyrosine (p = 0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in Km for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low Vmax) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

    Place, publisher, year, edition, pages
    Elsevier, 2009
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-6392 (URN)10.1016/j.neulet.2009.03.095 (DOI)000266360300012 ()19429160 (PubMedID)2-s2.0-67349103112 (Scopus ID)
    Available from: 2009-04-27 Created: 2009-04-27 Last updated: 2017-12-13Bibliographically approved
    2. Tryptophan transport in human fibroblast cells: a functional characterization
    Open this publication in new window or tab >>Tryptophan transport in human fibroblast cells: a functional characterization
    2011 (English)In: International Journal of Tryptophan Research, ISSN 1178-6469, no 4, p. 19-27Article in journal (Refereed) Published
    Abstract [en]

    There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.

    Tryptophan kinetic parameters (Vmax and Km) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of 3H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high Vmax and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower Vmax and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na+) dependent, while uptake at high substrate concentration was mainly Na+ independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.

    This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.

    Place, publisher, year, edition, pages
    Libertas Academica Ltd., 2011
    Keywords
    Fibroblasts, tryptophan, serotonin, LAT1, amino acid transporters
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-17365 (URN)10.4137/IJTR.S6913 (DOI)
    Available from: 2011-09-27 Created: 2011-09-27 Last updated: 2018-05-03Bibliographically approved
    3. Altered tryptophan and alanine transport in fibroblasts from boys with Attention Deficit/Hyperactivity Disorder (ADHD): an in vitro study
    Open this publication in new window or tab >>Altered tryptophan and alanine transport in fibroblasts from boys with Attention Deficit/Hyperactivity Disorder (ADHD): an in vitro study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-17366 (URN)
    Available from: 2011-09-27 Created: 2011-09-27 Last updated: 2017-10-17Bibliographically approved
    4. Decreased density of muscarinic acetylcholine receptors in fibroblasts from children with Attention Deficit/Hyperactivity Disorder (ADHD)
    Open this publication in new window or tab >>Decreased density of muscarinic acetylcholine receptors in fibroblasts from children with Attention Deficit/Hyperactivity Disorder (ADHD)
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-17367 (URN)
    Available from: 2011-09-27 Created: 2011-09-27 Last updated: 2017-10-17Bibliographically approved
    Download (pdf)
    omslag
    Download (pdf)
    spikblad
  • 4.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Landgren, Magnus
    Unit of Neurodevelopmental Disorders, Department of Paediatrics, Skaraborg Hospital, Mariestad, Sweden.
    Fernell, Elisabeth
    Unit of Neurodevelopmental Disorders, Department of Paediatrics, Skaraborg Hospital, Mariestad, Sweden; The Research and Development Centre, Skaraborg Hospital, Skövde, Sweden; The Gillberg Neuoropsychiatry Centre, Sahlgrenska Academy, Gothenburg, Sweden.
    Lewander, Tommy
    Department of Neuroscience, Psychiatry, Uppsala University Hospital, Uppsala, Sweden.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Decreased binding capacity (Bmax) of muscarinic acetylcholine receptors in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD)2013In: ADHD Attention Deficit and Hyperactivity Disorders, ISSN 1866-6116, E-ISSN 1866-6647, Vol. 5, no 3, p. 267-271Article in journal (Refereed)
    Abstract [en]

    Monoaminergic dysregulation is implicated in attention-deficit/hyperactivity disorder (ADHD), and methylphenidate and amphetamines are the most frequently prescribed pharmacological agents for treating ADHD. However, it has recently been proposed that the core symptoms of the disorder might be due to an imbalance between monoaminergic and cholinergic systems. In this study, we used fibroblast cell homogenates from boys with and without ADHD as an extraneural cell model to examine the cholinergic receptor density, that is, muscarinic acetylcholine receptors (mAChRs). We found that the binding capacity (Bmax) of [³H] Quinuclidinyl benzilate (³H-QNB) to mAChRs was decreased by almost 50 % in the children with ADHD (mean = 30.6 fmol/mg protein, SD = 25.6) in comparison with controls [mean = 63.1 fmol/mg protein, SD = 20.5, p ≤ 0.01 (Student's unpaired t test)]. The decreased Bmax indicates a reduced cholinergic receptor density, which might constitute a biomarker for ADHD. However, these preliminary findings need to be replicated in larger ADHD and comparison cohorts

    Download full text (pdf)
    fulltext
  • 5.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences.
    Landgren, Magnus
    Fernell, Elisabeth
    Vumma, Ravi
    Örebro University, School of Health and Medical Sciences.
    Ahlin, Arne
    Bjerkenstedt, Lars
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study2011In: Behavioral and Brain Functions, ISSN 1744-9081, E-ISSN 1744-9081, Vol. 7, p. 40-Article in journal (Refereed)
    Abstract [en]

    Background: The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport. Methods: Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V(max)) and affinity constant (K(m)) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test. Results: The ADHD group had significantly decreased V(max) (p = 0.039) and K(m) (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher V(max) of alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group. Conclusions: Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.

  • 6.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences.
    Landgren, Magnus
    Fernell, Elisabeth
    Vumma, Ravi
    Örebro University, School of Health and Medical Sciences.
    Åhlin, Arne
    Bjerkenstedt, Lars
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Altered tryptophan and alanine transport in fibroblasts from boys with Attention Deficit/Hyperactivity Disorder (ADHD): an in vitro studyManuscript (preprint) (Other academic)
  • 7.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences.
    Larsson, Christer
    Landgren, Magnus
    Fernell, Elisabeth
    Lewander, Tommy
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Decreased density of muscarinic acetylcholine receptors in fibroblasts from children with Attention Deficit/Hyperactivity Disorder (ADHD)Manuscript (preprint) (Other academic)
  • 8.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Vumma, Ravi
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Persson, M-L
    Karolinska Institutet, Stockholm, Sweden.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Aberrant tyrosine transport in fibroblasts from patients with bipolar type-1 disorder2010In: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 24, no 3, p. 364-365Article in journal (Refereed)
  • 9.
    Johansson, Jessica
    et al.
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Vumma, Ravi
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Interleukin-1beta inhibits tyrosine transport in fibroblasts from patients with schizophrenia and healthy controls2010In: Abstracts of, International Institute of Anticancer Research, 2010, no 3, p. 365-367, article id 45Conference paper (Refereed)
  • 10.
    Persson, Maj-Liz
    et al.
    Stockholm County Council, Center for Dependency Disorder, Karolinska University Hospital Huddinge.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences.
    Vumma, Ravi
    Örebro University, School of Health and Medical Sciences.
    Raita, Jani
    Stockholm County Council, Center for Dependency Disorder, Karolinska University Hospital Huddinge.
    Bjerkenstedt, Lars
    Psychiatry Section, Dept of Clinical and Experimental Medicine, Linköping University.
    Wiesel, Frits-Axel
    Department of Neuroscience, Psychiatry, University Hospital, Uppsala University.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Aberrant amino acid transport in fibroblasts from patients with bipolar disorder2009In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 457, no 1, p. 49-52Article in journal (Refereed)
    Abstract [en]

    Aberrant tyrosine transport is a repeated finding in fibroblasts from schizophrenic patients. The transport aberration could lead to disturbances in the dopaminergic and noradrenergic neurotransmitter systems. Tyrosine and tryptophan are the precursors of the neurotransmitters dopamine and serotonin. Disturbed dopaminergic, noradrenergic and serotoninergic systems are implicated as causes of bipolar disorder. Hence, the aim of this study was to explore whether patients with bipolar disorder have an aberrant transport of tyrosine and/or tryptophan. Fibroblast cell lines from patients with bipolar type-1 disorder (n = 10) and healthy controls (n = 10) were included in this study. All patients fulfilled the DSM-IV diagnostic criteria. The transport of amino acids across the cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport velocity (Vmax) and affinity constant (Km) were determined. A significantly lower Vmax for tyrosine (p = 0.027) was found in patients with bipolar type-1 disorder in comparison to healthy controls. No significant differences in Km for tyrosine and in the kinetic parameters of tryptophan between patients with bipolar type-1 disorder and healthy controls were observed. The decreased tyrosine transport (low Vmax) found in this study may indicate less access of dopamine in the brain, resulting in disturbed dopaminergic and/or noradrenergic neurotransmission, that secondarily could lead to disturbances in other central neurotransmitter systems, such as the serotoninergic system. However, as sample size was small in this study and an age difference between patients and controls existed, the present findings should be considered as pilot data. Further studies with larger sample number are needed to elucidate the transport aberration and the significance of these findings.

  • 11.
    Venizelos, Nikolaos
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Landgren, Magnus
    Dept Pediatrics, Skaraborg Hosp, Mariestad, Sweden.
    Fernell, Elisabeth
    Gillberg Neuoropsychiat Center, Sahlgrenska Academy, Gothenburg, Sweden.
    Lewander, T
    Uppsala University, Uppsala, Sweden.
    Decreased density of muscarinic acetylcholine receptors in fibroblast from boys with attention deficit/hyperactivity disorder (ADHD): An in vitro study2012In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 15, no s1, p. 224-224, article id P-17-015Article in journal (Refereed)
    Abstract [en]

    Background: It is believed that the neurotransmitters, dopamine and norepinephrine are involved in the pathophysiology of the neurobehavioral disorder Attention Deficit/Hyperactivity Disorder (ADHD). Moreover, it is known that cholinergic activity can modulate dopaminergic activity in the brain. The aim of this study was to measure the density and affinity of muscarinic acetylcholine receptors (mAChRs) in children with ADHD, by using the fibroblast cell model.

    Methods: Fibroblast cell homogenates from 11 boys with ADHD, fulfilling the DSM-IV diagnostic criteria and from 9 matching controls were used in the study. Radioligand binding assay was used to determine the maximal binding capacity (Bmax) and the equilibrium dissociation constant (KD) of mAChRs, using the mAChR antagonist 3H-QNB. Due to non-normally distribution of the calculated data, three outliers were identified by the MADE method (two in the ADHD group, both with a non-hereditary ADHD and one in the comparison group), and were therefore excluded from the statistical analyses.

    Results: A significantly lower Bmax for the binding of the muscarinic antagonist 3H-QNB was observed in the fibroblasts from the children with ADHD (n=9) when compared to controls (n=8) (p=0.01), but the KD did not differ between the two groups (p=0.40).

    Conclusions:The present results indicate a reduced density of mAChR in fibroblasts from children with a hereditary ADHD, which might be an indicator of the disorder. However, further studies are needed to confirm these observations.

  • 12.
    Venizelos, Nikolaos
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Landgren, Magnus
    Dept Pediatrics, Skaraborg Hosp, Mariestad, Sweden.
    Fernell, Elisabeth
    Gillberg Neuoropsychiat Center, Sahlgrenska Academy, Gothenburg, Sweden.
    Vumma, R
    Altered tryptophan and alanine transport in cultured fibroblast from boys with attention deficit/hyperactivity disorder (ADHD)2012In: International Journal of Neuropsychopharmacology, ISSN 1461-1457, E-ISSN 1469-5111, Vol. 15, no s1, p. 224-224, article id P-17-014Article in journal (Refereed)
    Abstract [en]

    Background: The amino acid tyrosine is the precursor for the synthesis of the neurotransmitters dopamine and norepinephrine, while tryptophan is the precursor of serotonin. These neurotransmitters are implicated in the pathophysiology of Attention Deficit/Hyperactivity Disorder (ADHD). A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other neuropsychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport. 

    Materials and Methods: Skin biopsies from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder were obtained, and from the biopsies were primary fibroblast cell lines derived. The transport of the amino acids tyrosine, tryptophan and alanine across the fibroblast cell membranes was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (Vmax) and affinity constant (Km) were determined. Student’s unpaired t-test or the Mann Whitney U test was used to analyze any difference between the two groups.

    Results: The tryptophan transport (Vmax) was significantly decreased in the ADHD group in comparison to controls (p=0.039), while the alanine transport (Vmax) was significantly increased in the ADHD group (p=0.031). There was no significant difference regarding the tyrosine transport between the two groups.

    Conclusions: A decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group, since tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.

  • 13.
    Vumma, Ravi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences.
    Lewander, Tommy
    Department of Neuroscience, Psychiatry, Ulleråker, Uppsala University Hospital.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Functional characterization of tryptophan transport in human fibroblast cellsManuscript (Other (popular science, discussion, etc.))
  • 14.
    Vumma, Ravi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences.
    Lewander, Tommy
    Department of Neuroscience, Psychiatry, Ulleråker, Uppsala University Hospital, Uppsala, Sweden.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Tryptophan transport in human fibroblast cells: a functional characterization2011In: International Journal of Tryptophan Research, ISSN 1178-6469, no 4, p. 19-27Article in journal (Refereed)
    Abstract [en]

    There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.

    Tryptophan kinetic parameters (Vmax and Km) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of 3H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high Vmax and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower Vmax and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na+) dependent, while uptake at high substrate concentration was mainly Na+ independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.

    This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.

    Download full text (pdf)
    fulltext
  • 15.
    Vumma, Ravi
    et al.
    Department of Chemistry and Biomedical Sciences, Faculty of Health and Life Sciences, Linnaeus University, Kalmar, Sweden.
    Johansson, Jessica
    Örebro University, School of Health Sciences.
    Venizelos, Nikolaos
    Örebro University, School of Medical Sciences.
    Proinflammatory Cytokines and Oxidative Stress Decrease the Transport of Dopamine Precursor Tyrosine in Human Fibroblasts2017In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 75, no 4, p. 178-184Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Proinflammatory cytokines and oxidative stress responses have been extensively implicated in the pathophysiology of neuropsychiatric disorders over the past 2 decades. Moreover, disturbed transport of the dopamine precursor (i.e., the amino acid tyrosine) has been demonstrated, in different studies, across fibroblast cell membranes obtained from neuropsychiatric patients. However, the role and influences of proinflammatory cytokines and oxidative stress, and the reasons for disturbed tyrosine transport in neuropsychiatric disorders, are still not evaluated.

    AIMS: The present study aimed to assess the role of proinflammatory cytokines and oxidative stress, indicated in many neuropsychiatric disorders, in tyrosine transportation, by using human skin-derived fibroblasts.

    METHODS: Fibroblasts obtained from a healthy control were used in this study. Fibroblasts were treated with proinflammatory cytokines (IL-1β, IFN-γ, IL-6, TNF-α), their combinations, and oxidative stress, optimized for concentrations and incubation time, to analyze the uptake of 14C-tyrosine compared to untreated controls.

    RESULTS AND CONCLUSION: This study demonstrates that proinflammatory cytokines and oxidative stress decrease the transport of tyrosine (47% and 33%, respectively), which can alter dopamine synthesis. The functionality of the tyrosine transporter could be a new potential biomarker to target for discovering new drugs to counteract the effects of proinflammatory cytokines and oxidative stress in the pathophysiology of neuropsychiatric disorders.

  • 16.
    Vumma, Ravi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jessica
    Örebro University, School of Health and Medical Sciences.
    Wiesel, F-A
    Bjerkenstedt, L.
    Venizelos, Nikolaos
    Örebro University, School of Health and Medical Sciences.
    Tyrosine transport through LAT1 transport system in fibroblasts of schizophrenic patients and healthy controlsManuscript (Other academic)
1 - 16 of 16
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf