| 1. |
- Ahmed, Aisha S., et al.
(författare)
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Activation of NF-kappa B in Synovium versus Cartilage from Patients with Advanced Knee Osteoarthritis : A Potential Contributor to Inflammatory Aspects of Disease Progression
- 2018
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 201:7, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to assess the activation and association of the NF-kappa B system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-kappa B subunit RelA in nuclear and cytosolic fractions and NF-kappa B1-DNA binding in nuclear extracts was assessed by ELISA, whereas NFKB1, RELA, IL-8, IL-6, and MMP3 gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues. We observed higher SM nuclear RelA protein levels and upregulated NF-kappa B1-DNA binding in OA patients compared with postmortem controls. However, in AC, lower nuclear RelA levels were observed compared with cytosolic extracts in patients. Nuclear RelA levels correlated positively with NF-kappa B1-DNA binding in SM and AC in patients. SM RELA and MMP3 mRNA levels were upregulated, whereas IL-8 and IL-6 as well as AC RELA were downregulated in patients compared with controls. In SM, nuclear RelA levels correlated positively with MMP3 gene expression in patients. A negative correlation was observed between SM nuclear RelA levels and AC NF-kappa B1-DNA binding, and SM nuclear NF-kappa B1-DNA binding correlated negatively with AC MMP3 and NFKB1 mRNA levels in patients. These findings highlight NF-kappa B-triggered cross-talk and feedback mechanisms between SM and AC in OA. Further, our findings strongly support a role for an activated NF-kappa B system in the transcriptional mechanism of inflammatory processes, especially in SM of patients with advanced OA.
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| 2. |
- Ahmed, Aisha S, et al.
(författare)
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NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease.
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
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| 3. |
- Alkass, Kanar, et al.
(författare)
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Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e69597-
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of unidentified bodies or suspected human remains is a frequent and important task for forensic investigators. However, any identification method requires clues to the person’s identity to allow for comparisons with missing persons. If such clues are lacking, information about the year of birth, sex and geographic origin of the victim, is particularly helpful to aid in the identification casework and limit the search for possible matches. We present here results of stable isotope analysis of 13C and 18O, and bomb-pulse 14C analyses that can help in the casework. The 14C analysis of enamel provided information of the year of birth with an average absolute error of 1.8±1.3 years. We also found that analysis of enamel and root from the same tooth can be used to determine if the 14C values match the rising or falling part of the bomb-curve. Enamel laydown times can be used to estimate the date of birth of individuals, but here we show that this detour is unnecessary when using a large set of crude 14C data of tooth enamel as a reference. The levels of 13C in tooth enamel were higher in North America than in teeth from Europe and Asia, and Mexican teeth showed even higher levels than those from USA. DNA analysis was performed on 28 teeth, and provided individual-specific profiles in most cases and sex determination in all cases. In conclusion, these analyses can dramatically limit the number of possible matches and hence facilitate person identification work.
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| 4. |
- Alkass, Kanar
(författare)
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External and intrinsic signatures in human teeth to assist forensic identification work
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In forensic medicine, dead victim identification constitutes an important task for forensic professionals including forensic pathologists, anthropologists, and odontologists. If no clues are at hand regarding the identity of the deceased, whether it is a victim of a mass disaster or a suspect homicide case, it is vital to know when a person died, and to know the sex and age of the decedent in order to limit the search for possible matching persons. In paper I, teeth from Swedish individuals were examined using both 14C analysis and aspartic acid racemization. The 14C analysis takes advantage of the so-called bombpulse, a tremendous increase of 14C in the atmosphere due to thousands of test detonations of nuclear weapons 1955-1963, which allows for an accurate birth dating of modern biological material. The aspartic acid racemization method gives an estimate of the age at death. The methods showed a significant correlation, and by combining them, we showed how both the year of birth and year of death of an unknown skeleton could be determined. In this study, we also found that14C levels in tooth enamel from Swedish teeth predicted the true date of birth with an average absolute error of 1.3 ± 0.9 years and that analysis of whole crown offered fairly good precision too. In paper II, the possibility of geographical differences in precision due to uneven distribution of bomb-pulse radiocarbon during the test bomb period was addressed. Interestingly, the 14C determinations predicted the true date of birth with a similar precision even when analyzing teeth from different continents. Conversely, the levels of the stable isotope 13C showed significant difference depending on geographical origin. In paper III, teeth were collected from North America to find out if differences in stable isotope concentrations can be detected in the teeth from subjects raised in such a limited geographical region. Teeth collected from subjects raised in Mexico showed extremely high 13C values, most likely due to a high consumption of corn and sugar cane. 13C levels in tooth roots were also higher in Mexican subjects compared with persons raised in United States and Canada, but the difference was not as conspicuous. Incorporation of 18O, another stable isotope, is mainly dependent on the drinking water. Analysis of 18O in tooth roots from subjects raised in Northwestern America showed the lowest levels, whereas this marker was not reliable for discriminating between Mexican and southern United States subjects. The 14C determinations of date of birth on North American teeth showed only slightly higher imprecision (average absolute error 1.8 ± 1.3 years) than Scandinavian teeth. In paper III, these and previous tooth 14C. Finally, a reference guide to birthdating persons using tooth 14C values is provided in paper III. In summary, these studies describe methods to determine date of birth, date of death, and origin of unknown dead victims, information that is expected to facilitate the identification work.
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| 5. |
- Bendel, Olof, et al.
(författare)
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Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension
- 2005
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1033:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.
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| 6. |
- Bergmann, Olaf, et al.
(författare)
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Dynamics of Cell Generation and Turnover in the Human Heart.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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| 7. |
- Bergmann, Olaf, et al.
(författare)
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Evidence for Cardiomyocyte Renewal in Humans
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5923, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
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| 8. |
- Bergmann, Olaf, et al.
(författare)
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Turnover of Human Cardiomyocytes
- 2008
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Ingår i: Circulation Research. - 0009-7330. ; 103:12, s. 1494-1495
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Konferensbidrag (refereegranskat)
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| 9. |
- Clara, Alfsdotter, et al.
(författare)
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Development and implementation of forensic anthropology in Swedish forensic practice
- 2022
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Ingår i: Scandinavian Journal of Forensic Science. - : Sciendo. - 2353-0707. ; 28:Supplement 1, s. 10-19
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the ongoing development of forensic anthropology in Sweden. We discuss the background of the discipline, its application, as well as its current and potential development in Swedish forensic practice. Collaboration with osteoarchaeologists in skeletal forensic cases has a long tradition in Sweden. Analyses of skeletal remains are performed ad-hoc, in contrast to analyses of fleshed human remains. While several law enforcement employees are educated in forensic anthropology and /or osteoarchaeology , they are not employed in these fields, and regional variations are evident. Internationally, forensic anthropology has become an autonomous forensic discipline over the past decades, requiring skills beyond mere skeletal analysis. To keep on a par with international standards, it may be time to revisit the concept of forensic anthropology in Sweden. Despite the limited presence of supporting organisational structures and systems, forensic anthropological and hard-tissue-reliant physico-chemical analyses have proven valuable in Swedish forensic practice, especially in cases of personal identification, trauma analysis and search efforts. We argue that Sweden could benefit from making qualified forensic anthropology expertise available in all law enforcement regions, starting to implement and promote forensic anthropology in routine forensic casework and formalising the role of forensic anthropology practitioners.
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| 10. |
- Druid, Henrik, et al.
(författare)
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Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis
- 2007
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 168:2-3, s. 223-226
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Tidskriftsartikel (refereegranskat)abstract
- In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.
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| 11. |
- Ernst, Aurélie, et al.
(författare)
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Neurogenesis in the Striatum of the Adult Human Brain
- 2014
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Ingår i: Cell. - Cambridge, MA 02139, USA : Elsevier. - 0092-8674 .- 1097-4172. ; 156:5, s. 1072-1083
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Tidskriftsartikel (refereegranskat)abstract
- Neurons are added throughout life in the hippocampus and olfactory bulb in most mammals, although humans represent an exception without detectable olfactory bulb neurogenesis. Nevertheless, neuroblasts are generated in the lateral ventricle wall in humans, the neurogenic niche for olfactory bulb neurons in other mammals. We show that, in humans, new neurons integrate adjacent to this neurogenic niche, in the striatum. The neuronal turnover in the striatum appears restricted to interneurons and we show that postnatally generated striatal neurons are preferentially depleted in Huntington’s disease. This demonstrates a unique pattern of neurogenesis in the adult human brain.
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| 12. |
- Heinke, Paula, et al.
(författare)
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Diploid hepatocytes drive physiological liver renewal in adult humans
- 2022
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Ingår i: CELL SYSTEMS. - : Elsevier. - 2405-4712 .- 2405-4720. ; 13:6, s. 499-
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Tidskriftsartikel (refereegranskat)abstract
- Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (C-14) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.
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| 13. |
- Kononenko, Olga, et al.
(författare)
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Opioid precursor protein isoform is targeted to the cell nuclei in the human brain
- 2017
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434 .- 0304-4165 .- 1872-8006. ; 1861:2, s. 246-255
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the κ-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms. We here searched for novel PDYN mRNA and their protein product in the human brain.METHODS: Novel PDYN transcripts were identified using nested PCR amplification of oligo(dT) selected full-length capped mRNA. Gene expression was analyzed by qRT-PCR, PDYN protein by western blotting and confocal imaging, dynorphin peptides by radioimmunoassay. Neuronal nuclei were isolated using fluorescence-activated nuclei sorting (FANS) from postmortem human striatal tissue. Immunofluorescence staining and confocal microscopy was performed for human caudate nucleus.RESULTS: Two novel human PDYN mRNA splicing variants were identified. Expression of one of them was confined to the striatum where its levels constituted up to 30% of total PDYN mRNA. This transcript may be translated into ∆SP-PDYN protein lacking 13 N-terminal amino acids, a fragment of signal peptide (SP). ∆SP-PDYN was not processed to mature dynorphins and surprisingly, was targeted to the cell nuclei in a model cellular system. The endogenous PDYN protein was identified in the cell nuclei in human striatum by western blotting of isolated neuronal nuclei, and by confocal imaging.CONCLUSIONS AND GENERAL SIGNIFICANCE: High levels of alternatively spliced ∆SP-PDYN mRNA and nuclear localization of PDYN protein suggests a nuclear function for this isoform of the opioid peptide precursor in human striatum.
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| 14. |
- Kugelberg, Fredrik, 1974-, et al.
(författare)
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Influence of blood loss on the pharmacokinetics of citalopram
- 2006
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 161:2-3, s. 163-168
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Tidskriftsartikel (refereegranskat)abstract
- Extended blood loss results in several compensatory physiological mechanisms, including transfer of extravascular fluid into the blood circulation. If drugs are present in the body, this fluid exchange may imply that blood drug concentrations found in a trauma victim may differ from the concentrations present at the time of the trauma. To address this issue, an animal model was used to investigate the influence of blood loss on pre-existing levels of the antidepressant drug citalopram and its demethylated metabolites. Rats were administered citalopram either acutely (40 mg/kg, orally) or chronically (20 mg/kg daily, subcutaneously) for 6 days using osmotic pumps. In the experimental rats, blood loss was accomplished by withdrawing 0.8 mL blood at 10 min intervals during 70 min. In the control rats, blood was withdrawn at 0 and 70 min only. Blood, brain and lung drug concentrations were analyzed with an enantioselective HPLC method. In the chronically treated rats, the ratios between final and initial citalopram concentrations were 1.08 ± 0.15 and 1.01 ± 0.09 in the experimental rats and controls, respectively, indicating no major effect of blood loss. In contrast, acute oral administration resulted in increased ratios in the exsanguinated rats as compared to controls (1.84 ± 0.50 versus 0.73 ± 0.07, p = 0.0495). In conclusion, the observation of increased blood drug levels in the acute oral rats indicates that absorption of fluid from the gastrointestinal tract may be important in the intravascular refill. Further, in the interpretation of post-mortem blood levels of drugs, these physiological mechanisms should be taken into account. © 2006 Elsevier Ireland Ltd. All rights reserved.
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| 15. |
- Quintana, Hedley Knewjen, et al.
(författare)
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Comorbidities in relation to fatali of first myocardial infarction
- 2018
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Ingår i: Cardiovascular pathology. - : ELSEVIER SCIENCE INC. - 1054-8807 .- 1879-1336. ; 32, s. 32-37
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Present knowledge concerning potential associations between comorbidities and the fatality of a first myocardial infarction (MI) is limited.Aim: To identify comorbidities in 45-70-year-old individuals who suffered a first MI and died within 7 days in Stockholm County from 1992-1994. In addition, to assess how each of the comorbidities identified, as well as the number of hospitalizations during the 10-year period prior to the MI, was associated with MI fatality.Methods: The data collected on our inception cohort of 1984 first Ml, of which 524 were fatal within 7 days, were primarily self-reported, proxy-reported by questionnaire and/or extracted from comprehensive national registers. Comorbidilies among fatal cases with a prevalence >2% were identified. Risk ratios (with 95% confidence intervals) for the association of Ml fatality with number of prior hospitalizations and specific comorbidities were calculated using binomial regression with log link. A structured review of autopsy reports on fatal cases was performed in order to identify additional indicators of comorbidities.Results: After adjusting for sex, age and disposable income, the number of previous hospitalizations was associated with 7-day Ml fatality. Of the comorbidities identified as prevalent in fatal cases, the following were associated with 7-day fatality in crude analysis: epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes, and rheumatoid arthritis. Indicators of comorbidities identified from autopsy data included a silent MI, severe atherosclerosis of the abdominal aorta, and hepatic steatosis. Adjustments for sex and age (although not possible for epilepsy and alcoholism), did not substantially alter results.Conclusions: Our current findings indicate that in connection with a first MI, particular attention should be paid to those with repeated prior hospitalizations and/or epilepsy, heart failure, stroke, alcoholism, cancer, renal diseases, asthma, psychiatric diseases, diabetes and rheumatoid arthritis.
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| 16. |
- Reu, Pedro, et al.
(författare)
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The Lifespan and Turnover of Microglia in the Human Brain
- 2017
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Ingår i: Cell Reports. - Cambridge, MA 02139, USA : Elsevier BV. - 2211-1247. ; 20:4, s. 779-784
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Tidskriftsartikel (refereegranskat)abstract
- The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.
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| 17. |
- Sjölin, Karl, et al.
(författare)
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Distribution of five clinically important neuroglial proteins in the human brain.
- 2022
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Ingår i: Molecular brain. - : Springer Nature. - 1756-6606. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.
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| 18. |
- Spaulding, Kirsty, et al.
(författare)
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Dynamics of Hippocampal Neurogenesis in Adult Humans
- 2013
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Ingår i: Cell. - Maryland Heights, MO, USA : Elsevier. - 0092-8674 .- 1097-4172. ; 153:6, s. 1219-1227
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Tidskriftsartikel (refereegranskat)abstract
- Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have func- tional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear- bomb-test-derived 14C in genomic DNA, and we present an integrated model of the cell turnover dy- namics. We found that a large subpopulation of hip- pocampal neurons constituting one-third of the neu- rons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neu- rons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neuro- genesis may contribute to human brain function.
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| 19. |
- Strandberg, Joakim J, et al.
(författare)
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Toxicological analysis in rats subjected to heroin and morphine overdose
- 2006
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Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 166:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- In heroin overdose deaths the blood morphine concentration varies substantially. To explore possible pharmacokinetic explanations for variable sensitivity to opiate toxicity we studied mortality and drug concentrations in male Sprague-Dawley rats. Groups of rats were injected intravenously (i.v.) with heroin, 21.5 mg/kg, or morphine, 223 mg/kg, causing a 60–80% mortality among drug-naïve rats. Additional groups of rats were pre-treated with morphine for 14 days, with or without 1 week of subsequent abstinence. Brain, lung and blood samples were analyzed for 6-acetylmorphine, morphine, morphine-3-glucuronide and morphine-6-glucuronide. i.v. morphine administration to drug-naïve rats resulted in both rapid and delayed deaths. The brain morphine concentration conformed to an exponential elimination curve in all samples, ruling out accumulation of morphine as an explanation for delayed deaths. This study found no support for formation of toxic concentration of morphine-6-glucuronide. Spontaneous death among both heroin and morphine rats occurred at fairly uniform brain morphine concentrations. Morphine pre-treatment significantly reduced mortality upon i.v. morphine injection, but the protective effect was less evident upon i.v. heroin challenge. The morphine pre-treatment still afforded some protection after 1 week of abstinence among rats receiving i.v. morphine, whereas rats given i.v. heroin showed similar death rate as drug-naïve rats.
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| 20. |
- Taqi, Malik Mumtaz, et al.
(författare)
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Prodynorphin CpG-SNPs associated with alcohol dependence : elevated methylation in the brain of human alcoholics
- 2011
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 16:3, s. 499-509
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Tidskriftsartikel (refereegranskat)abstract
- The genetic, epigenetic and environmental factors may influence the risk for neuropsychiatric disease through their effects on gene transcription. Mechanistically, these effects may be integrated through regulation of methylation of CpG dinucleotides overlapping with single-nucleotide polymorphisms (SNPs) associated with a disorder. We addressed this hypothesis by analyzing methylation of prodynorphin (PDYN) CpG-SNPs associated with alcohol dependence, in human alcoholics. Postmortem specimens of the dorsolateral prefrontal cortex (dl-PFC) involved in cognitive control of addictive behavior were obtained from 14 alcohol-dependent and 14 control subjects. Methylation was measured by pyrosequencing after bisulfite treatment of DNA. DNA binding proteins were analyzed by electromobility shift assay. Three PDYN CpG-SNPs associated with alcoholism were found to be differently methylated in the human brain. In the dl-PFC of alcoholics, methylation levels of the C, non-risk variant of 3'-untranslated region (3'-UTR) SNP (rs2235749; C > T) were increased, and positively correlated with dynorphins. A DNA-binding factor that differentially targeted the T, risk allele and methylated and unmethylated C allele of this SNP was identified in the brain. The findings suggest a causal link between alcoholism-associated PDYN 3'-UTR CpG-SNP methylation, activation of PDYN transcription and vulnerability of individuals with the C, non-risk allele(s) to develop alcohol dependence.
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| 21. |
- Teglind, Rebecka, et al.
(författare)
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Analysis of C-14, C-13 and Aspartic Acid Racemization in Teeth and Bones to Facilitate Identification of Unknown Human Remains : Outcomes of Practical Casework
- 2021
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- The identification of unknown human remains represents an important task in forensic casework. If there are no clues as to the identity of the remains, then the age, sex, and origin are the most important factors to limit the search for a matching person. Here, we present the outcome of application of so-called bomb pulse radiocarbon (C-14 derived from above-ground nuclear bomb tests during 1955-1963) analysis to birthdate human remains. In nine identified cases, C-14 analysis of tooth crowns provided an estimate of the true date of birth with an average absolute error of 1.2 & PLUSMN; 0.8 years. Analysis of C-14 in tooth roots also showed a good precision with an average absolute error of 2.3 & PLUSMN; 2.5 years. Levels of C-14 in bones can determine whether a subject has lived after 1955 or not, but more precise carbon turnover data for bones would be needed to calculate date of birth and date of death. Aspartic acid racemization analysis was performed on samples from four cases; in one of these, the year of birth could be predicted with good precision, whereas the other three cases are still unidentified. The stable isotope C-13 was analyzed in tooth crowns to estimate provenance. Levels of C-13 indicative of Scandinavian provenance were found in known Scandinavian subjects. Teeth from four Polish subjects all showed higher C-13 levels than the average for Scandinavian subjects.
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| 22. |
- Watanabe, Hiroyuki, et al.
(författare)
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Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate : a Putative Molecular Basis for Lateralization of Emotions and Pain
- 2015
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Ingår i: Cerebral Cortex. - United kingdom : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 25:1, s. 97-108
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Tidskriftsartikel (refereegranskat)abstract
- Lateralization of processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria and pain, the m-, d- and k-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and five “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg and Met-enkephalin-Arg-Phe, preferential d-/m- and k-/m-opioid agonists demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B strongly correlated with Leu-enkephalin-Arg in the left but not right ACC suggesting different mechanisms of conversion of this k-opioid agonist to d-/m-opioid ligand in the two hemispheres; in the right ACC dynorphin B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlyes in part lateralization of higher functions including positive and negative emotions and pain in the human brain.
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| 23. |
- Yeung, Maggie, et al.
(författare)
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Dynamics of Oligodendrocyte Generation and Myelination in the Human Brain
- 2014
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Ingår i: Cell. - Maryland Heights : Elsevier. - 0092-8674 .- 1097-4172. ; 159:4, s. 766-774
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Tidskriftsartikel (refereegranskat)abstract
- The myelination of axons by oligodendrocytes has been suggested to be modulated by experience, which could mediate neural plasticity by optimizing the performance of the circuitry. We have assessed the dynamics of oligodendrocyte generation and myelination in the human brain. The number of oligodendrocytes in the corpus callosum is established in childhood and remains stable after that. Analysis of the integration of nuclear bomb test-derived 14C revealed that myelin is exchanged at a high rate, whereas the oligodendrocyte population in white matter is remarkably stable in humans, with an annual exchange of 1/300 oligodendrocytes. We conclude that oligodendrocyte turnover contributes minimally to myelin remodeling in human white matter and that this instead may be carried out by mature oligodendrocytes, which may facilitate rapid neural plasticity.
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| 24. |
- Zilg, Brita, et al.
(författare)
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A Rapid Method for Postmortem Vitreous Chemistry - Deadside Analysis
- 2022
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Vitreous fluid is commonly collected for toxicological analysis during forensic postmortem investigations. Vitreous fluid is also often analyzed for potassium, sodium, chloride and glucose for estimation of time since death, and for the evaluation of electrolyte imbalances and hyperglycemia, respectively. Obtaining such results in the early phase of a death investigation is desirable both in regard to assisting the police and in the decision-making prior to the autopsy. We analyzed vitreous fluid with blood gas instruments to evaluate/examine the possible impact of different sampling and pre-analytical treatment. We found that samples from the right and left eye, the center of the eye as well as whole vitreous samples gave similar results. We also found imprecision to be very low and that centrifugation and dilution were not necessary when analyzing vitreous samples with blood gas instruments. Similar results were obtained when analyzing the same samples with a regular multi-analysis instrument, but we found that such instruments could require dilution of samples with high viscosity, and that such dilution might impact measurement accuracy. In conclusion, using a blood gas instrument, the analysis of postmortem vitreous fluid for electrolytes and glucose without sample pretreatment produces rapid and reliable results.
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