1.
Regland, Björn, 1947
(författare)
Schizophrenia and single-carbon metabolism
2005
Ingår i: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY. - : Elsevier BV. - 0278-5846. ; 29:7, s. 1124-1132
Forskningsöversikt (refereegranskat)
2.
Roman, Erika, et al.
(författare)
Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats
2005
Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 29:4, s. 591-601
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. METHODS: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. RESULTS: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. CONCLUSIONS: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown.
3.
Lindquist, Catarina
(författare)
Physiology and Pharmacology of GABAA receptors: The Brakes in the Brain
2005
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Inhibitory neurotransmission in the brain is mostly mediated by gamma-aminobutyric acid type A (GABAA) receptors. These receptors are involved in both phasic inhibition (point-to-point inhibition, synaptic transmission) and tonic inhibition (diffuse form of inhibition, brain homeostasis). In this thesis the functional and pharmacological properties of GABAA receptors expressed in brain slices or in Sf 9 cells were studied. GABAA receptors expressed extrasynaptically are believed to be involved in tonic inhibition. In hippocampal dentate gyrus granule cells we identified and characterized three types of extrasynaptic receptor types (GABARex) that varied in their affinity for GABA, maximal single-channel conductance and sensitivity to drugs. For the first time we showed how the GABA concentration determines the conductance of GABAA receptors in brain tissue. There is thus a direct link between the extracellular GABA concentration and the level of the tonic inhibition, providing dynamic control. It is only within the last ten years or so that the tonic inhibition was discovered and only recently has it gained widespread interest. One reason is that it has become quite clear that the first site of action and probably often the most important site of action of drugs are the extrasynaptic receptors. We found that a drug now in clinical trials (THIP) at the clinically relevant concentration activates these extrasynaptic receptors. It has been assumed that spontaneous openings of the receptors are only functionally significant in receptor complexes containing the epsilon-subunit or mutations. We show that alpha/beta and alpha/beta/gamma?receptors can open spontaneously and be modified by drugs. The capacity to open spontaneously may be vital for fast responses such as at synapses. This suggests that the functional properties of receptors located at synapses and outside of synapses (extrasynaptic receptors: GABARex) differ. Those at synapses open rapidly (ms) whereas those at extrasynaptic sites open after a delay of ten to hundreds of seconds. This functional difference is very important in terms of brain function as it ensures fast flow of information (synaptic transmission) but in a controlled way that is set by the gain and the time window for synaptic transmission integration via the tonic inhibition. By using the compound SR95531, we constructed a model that accounts for activation and inhibition of both phasic- and tonic-like currents in an expression system. This model can be used to calculate what concentrations of the inhibitor to use to specifically block certain GABARex receptors in brain tissue to study how a particular population of GABARex contributes to the tonic inhibition and how it affects both excitatory and inhibitory synaptic transmission.
4.
Lindström, L, et al.
(författare)
Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia.
2005
Ingår i: Schizophrenia research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 80:2-3, s. 315-22
Tidskriftsartikel (refereegranskat) abstract
Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n=49) and male patients with schizophrenia (n=90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM+/-0.10 vs. 1.06 nM+/-0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM+/-0.19, n=37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM+/-0.17, n=34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM+/-0.10, n=19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.
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7.
Andersen, Grethe, et al.
(författare)
Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes
2005
Ingår i: Scandinavian Journal of Immunology. - Oxford : Wiley. - 0300-9475 .- 1365-3083. ; 61:3, s. 279-284
Tidskriftsartikel (refereegranskat) abstract
Levels of the melanocortin receptor (MCR) 1, 2, 3 and 5 subtypes and pro-opio-melanocortin (POMC) protein mRNA were measured by the real-time quantitative reverse transcriptase polymerase chain reaction method in CD4+ T helper (Th) cells, CD8+ T cytotoxic cells, CD19+ B cells, CD56+ natural killer (NK) cells, CD14+ monocytes and CD15+ granulocytes from healthy donors. We found high levels of all of the MC1, 2, 3 and 5R subtype mRNA in Th cells and moderate levels in NK cells, monocytes and granulocytes. POMC peptide mRNA was found in all examined leucocyte subsets, but only low levels were present in granulocytes. Our findings suggest a co-ordinating role for MCR subtypes and their naturally occurring ligands in the co-operation between innate and adaptive immunity. Moreover, our findings are compatible with earlier finding of MCR-mediated tolerance induction in Th cells.
8.
García Rodríguez, LA, et al.
(författare)
Risk factors for inflammatory bowel disease in the general population
2005
Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 22:4, s. 309-315
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND The aetiology of inflammatory bowel disease remains largely unknown. AIM We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. METHODS We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. RESULTS Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). CONCLUSIONS Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.
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