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- Forsberg, A., et al.
(författare)
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The Immune Response of the Human Brain to Abdominal Surgery
- 2017
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
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| 3. |
- Andersson, M, et al.
(författare)
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Serotonin transporter availability in adults with autism-a positron emission tomography study
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:5, s. 1647-1658
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Tidskriftsartikel (refereegranskat)abstract
- Impairments in social interaction and communication, in combination with restricted, repetitive behaviors and interests, define the neurodevelopmental diagnosis of autism spectrum disorder (ASD). The biological underpinnings of ASD are not well known, but the hypothesis of serotonin (5-HT) involvement in the neurodevelopment of ASD is one of the longest standing. Reuptake through the 5-HT transporter (5-HTT) is the main pathway decreasing extracellular 5-HT in the brain and a marker for the 5-HT system, but in vivo investigations of the 5-HTT and the 5-HT system in ASD are scarce and so far inconclusive. To quantify possible alterations in the 5-HT system in ASD, we used positron emission tomography and the radioligand [11C]MADAM to measure 5-HTT availability in the brain of 15 adults with ASD and 15 controls. Moreover, we examined correlations between regional 5-HTT availability and behavioral phenotype assessments regarding ASD core symptoms. In the ASD group, we found significantly lower 5-HTT availability in total gray matter, brainstem, and 9 of 18 examined subregions of gray matter. In addition, several correlations between regional 5-HTT availability and social cognitive test performance were found. The results confirm the hypothesis that 5-HTT availability is lower in the brain of adult individuals with ASD, and are consistent with the theory of 5-HT involvement in ASD neurodevelopment. The findings endorse the central role of 5-HT in the physiology of ASD, and confirm the need for a continued investigation of the 5-HT system in order to disentangle the biology of ASD.
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| 5. |
- Borg, J., et al.
(författare)
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Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain
- 2016
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Ingår i: Molecular Psychiatry. - London, United Kingdom : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 51, s. 879-879
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.
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