| 1. |
- Agardh, Carl-David, et al.
(författare)
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Free radical production and ischemic brain damage: influence of postischemic oxygen tension
- 1991
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 1873-474X .- 0736-5748. ; 9:2, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred. In conclusion, there was thus no indication that variations in the postischemic oxygen supply altered production of free radicals, or modulated the damage incurred as a result of the ischemia. We conclude that free radical production may not be an important factor in the pathogenesis of brain damage following brief periods of ischemia, but may represent an important modulator following longer periods of ischemia, when a vascular component becomes an important factor in the pathological events.
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| 6. |
- af Bjerkén, Sara, et al.
(författare)
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Inhibition of astrocytes promotes long-distance growing nerve fibers in ventral mesencephalic cultures
- 2008
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 26:7, s. 683-691
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Tidskriftsartikel (refereegranskat)abstract
- Tyrosine hydroxylase-positive nerve fiber formation occurs in two diverse morphological patterns in rat fetal ventral mesencephalic slice cultures; one is non-glial-associated and the other is glial-associated. The aim of this study was to characterize the non-glial-associated nerve fibers and its relation to migration of astrocytes. Organotypic slice cultures were prepared from embryonic days 12, 14, and 18 rat fetuses and maintained for 5, 7 or 14 days in vitro. Inhibition of cell proliferation using cytosine beta-D-arabinofuranoside was conducted in embryonic day 14 ventral mesencephalic cultures. The treatment impaired astrocytic migration at 7 and 14 days in vitro. The reduced migration of astrocytes exerted a negative effect on the glial-associated tyrosine hydroxylase-positive nerve fibers, reducing the outgrowth from the tissue slice. The non-glial-associated outgrowth was, however, positively affected by reduced astrocytic migration, reaching distances around 3mm in 2 weeks, and remained for longer time in culture. Co-cultures of fetal ventral mesencephalon and frontal cortex revealed the cortex as a target for the non-glial-associated tyrosine hydroxylase-positive outgrowth. The age of the fetal tissue at plating affected the astrocytes such that older tissue increased the length of astrocyte migration. Younger tissue at plating promoted the presence of non-glial-associated outgrowth and long radial-glia-like processes, while older tissue promoted migration of neurons instead of formation of nerve fiber network. In conclusion, inhibition of astrocytic proliferation promotes the persistence of long-distance growing tyrosine hydroxylase-positive nerve fibers in ventral mesencephalic slices cultures. Furthermore, the long-distance growing nerve fibers target the frontal cortex and are absent in cultures derived from older tissue.
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| 13. |
- Koning, Gabriella, et al.
(författare)
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Magnesium sulphate induces preconditioning in preterm rodent models of cerebral hypoxia-ischemia.
- 2018
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Ingår i: International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. - : Wiley. - 1873-474X. ; 70, s. 56-66
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Tidskriftsartikel (refereegranskat)abstract
- Brain injury in preterm infants represents a substantial clinical problem associated with development of motor impairment, cognitive deficits and psychiatric problems. According to clinical studies, magnesium sulphate (MgSO4) given to women in preterm labor reduces the risk of cerebral palsy in the offspring but the mechanisms behind its neuroprotective effects are still unclear. Our aim was to explore whether MgSO4 induces tolerance (preconditioning) in the preterm rodent brain. For this purpose we established a model of perinatal hypoxia-ischemia (HI) in postnatal day 4 rats and also applied a recently developed postnatal day 5 mouse model of perinatal brain injury.Postnatal day 4 Wistar rats were exposed to unilateral carotid artery ligation followed by 60, 70 or 80min of hypoxia (8% O2). On postnatal day 11, brains were collected and macroscopically visible damage as well as white and grey matter injury was examined using immunohistochemical staining. Once the model had been established, a possible preconditioning protection induced by a bolus MgSO4 injection prior to 80min HI was examined 7days after the insult. Next, a MgSO4 bolus was injected in C57Bl6 mice on PND 4 followed by exposure to unilateral carotid artery ligation and hypoxia, (10% O2) for 70min on PND 5. Brains were collected 7days after the insult and examined with immunohistochemistry for grey and white matter injury.In rats, a 60min period of hypoxia resulted in very few animals with brain injury and although 70min of hypoxia resulted in a higher percentage of injured animals, the brains were marginally damaged. An 80min exposure of hypoxia caused cortical tissue damage combined with hippocampal atrophy and neuronal loss in the C3 hippocampal layer. In the rat model, MgSO4 (1.1mg/g administered i.p. 24h prior to the induction of HI, resulting in a transient serum Mg2+ concentration elevation to 4.1±0.2mmol/l at 3h post i.p. injection) reduced brain injury by 74% in grey matter and 64% in white matter. In the mouse model, MgSO4 (0.92mg/g) i.p. injection given 24h prior to the HI insult resulted in a Mg2+ serum concentration increase reaching 2.7±0.3mmol/l at 3h post injection, which conferred a 40% reduction in grey matter injury.We have established a postnatal day 4 rat model of HI for the study of preterm brain injury. MgSO4 provides a marked preconditioning protection both in postnatal day 4 rats and in postnatal day 5 mice.
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| 14. |
- Linhares, Sara Sophia Guedes, et al.
(författare)
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Effects of prenatal exposure to fluoxetine on circadian rhythmicity in the locomotor activity and neuropeptide Y and 5-HT expression in male and female adult Wistar rats
- 2022
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Ingår i: International Journal of Developmental Neuroscience. - : John Wiley & Sons. - 0736-5748 .- 1873-474X. ; 82:5, s. 407-422
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin (5-HT) reuptake inhibitors, such as fluoxetine, are the most prescribed antidepressant for maternal depression. In this sense, it exposes mothers and the brains of infants to increased modulatory and trophic effects of serotonergic neurotransmission. 5-HT promotes essential brain changes throughout its development, which include neuron migration, differentiation and organisation of neural circuitries related to emotional, cognitive and circadian behavior. Early exposure to the SSRIs induces long-term effects on behavioral and neural serotonergic signalisation. We have aimed to evaluate the circadian rhythm of locomotor activity and the neurochemical content, neuropeptide Y (NPY) and 5-HT in three brain areas: intergeniculate leaflet (IGL), suprachiasmatic nuclei (SCN) and raphe nuclei (RN), at two zeitgebers (ZT6 and ZT18), in male and female rat's offspring early exposed (developmental period GD13-GD21) to fluoxetine (20 mg/kg). First, we have conducted daily records of the locomotor activity rhythm using activity sensors coupled to individual cages over 4 weeks. We have lastly evaluated the immunoreactivity of NPY in both SCN and IGL, as well the 5-HT expression in the dorsal and medial RN. In summary, our results showed that (1) prenatal fluoxetine affects phase entrainment of the rest/activity rhythm at ZT6 and ZT18, more in male than female specimens, and (2) modulates the NPY and 5-HT expression. Here, we show male rats are more susceptible to phase entrainment and the NPY and 5-HT misexpression compared to female ones. The sex differences induced by early exposure to fluoxetine in both the circadian rhythm of locomotor activity and the neurochemical expression into SCN, IGL and midbrain raphe are an important highlight in the present work. Thus, our results may help to improve the knowledge on neurobiological mechanisms of circadian rhythms and are relevant to understanding the "broken brains" and behavioral abnormalities of offspring early exposed to antidepressants.
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| 17. |
- Miller, Marilyn T, et al.
(författare)
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Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review.
- 2005
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 23:2-3, s. 201-219
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Tidskriftsartikel (refereegranskat)abstract
- Autism is a complex developmental disorder without an established single etiology but with significant contributions from genetic studies, functional research, and neuropsychiatric and neuroradiologic investigations. The purpose of this paper is to review the findings in five studies involving individuals manifesting the characteristic findings of autism spectrum disorder associated with malformations and dysfunctions known to result from early embryogenic defects. These investigations include two associated with teratogens (thalidomide embryopathy, Mobius sequence with misoprostol) and three (most Mobius sequence cases, CHARGE association, Goldenhar syndrome) with no known etiology. These studies suggest that early embryonic development errors often involving cranial nerve palsies, internal and external ear malformations, ophthalmologic anomalies, and a variety of systemic malformations may be associated with autism spectrum disorders statistically more frequently than expected in a normal population. Although the exact time of developmental insult for each condition cannot be identified, the evidence is that it may occur as early as week 4 to 6+ of embryogenesis.
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| 18. |
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| 20. |
- Oreland, Sadia, et al.
(författare)
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Prolonged maternal separation decreases granule cell number in the dentate gyrus of 3-week-old male rats
- 2010
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 28:2, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- Maternal separation (MS) early in life affects many aspects of development and we have previously observed significant decreases in NMDA and AMPA receptor and elevated glutamate transporter expression in the hippocampus of MS360 animals relative to MS15. We hypothesized that this disruption of the glutamatergic system in adult animals was a sign of a reduction in hippocampal neuronal number in 3-week-old animals. Male Wistar rat pups were separated litter-wise for 15 min (MS15) or 360 min (MS360) from postnatal day 1 to 21. Conventional laboratory reared animals were also included. At postnatal day 22, brains were dissected and sliced on a cryostat. Immunohistochemistry labeled neurons (NeuN) and astrocytes (GFAP) and the number of neurons was quantified using the disector method and Cavalieri principle for stereology for the CA1, CA2, CA3 and dentate gyrus regions of the hippocampus. The volume of 4 regions did not differ across the 3 experimental groups. Numerical density of neurons, however, was significantly different in CA3 (one-way ANOVA; p=0.044) and the dentate gyrus (one-way ANOVA; p<0.0001) with post hoc differences MS360 vs. MS15. Finally, the total number of neurons was calculated and MS360 animals had significantly fewer neurons than MS15 animals in the dentate gyrus. Therefore, the maternal separation procedure affected development of the hippocampus directly at 3 weeks of age. The differences observed consequently place young MS360 animals in a vulnerable state for challenges later in life.
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| 21. |
- Philippot, Gaetan, et al.
(författare)
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Evaluation of the dentate gyrus in adult mice exposed to acetaminophen (paracetamol) on postnatal day 10
- 2021
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Ingår i: International Journal of Developmental Neuroscience. - : John Wiley & Sons. - 0736-5748 .- 1873-474X. ; 81:1, s. 91-97
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (AAP; or paracetamol) is a widely used nonprescription drug with antipyretic and analgesic properties. Alarmingly, there is an increasing body of evidence showing that developmental exposure to AAP is associated with adverse behavioural outcomes later in life. We have previously shown that relevant doses of AAP in 10-day-old mice affected memory, learning and locomotor activity in the adult animals. Interestingly, the neurons of the dentate gyrus (DG) have a relatively late time of origin as they are generated during the first two weeks of postnatal life in rodents. Since the generation of these cells, which are important for memory processing, coincides with our AAP exposure, we aim to investigate if the cytoarchitecture of the DG is affected by postnatal day 10 AAP treatment. In addition, we investigate if markers for differentiation and migration in the hippocampus were affected by the same treatment. We did not observe any visual effects in adult DG cytoarchitecture, nor any changes of markers for differentiation/migration in the hippocampus in 24 hr after exposure. Even though a large effect size was estimated on adult DG thickness following AAP exposure, the estimated 95% CIs around the differences of the means reveal no significant effect. Hence, larger sample sizes are warranted to clarify if neonatal AAP exposure affects adult DG thickness in mice.
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| 22. |
- Pierzynowski, Stefan, et al.
(författare)
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Impact of colostrum and plasma immunoglobulin intake on hippocampus structure during early postnatal development in pigs.
- 2014
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 1873-474X .- 0736-5748. ; 35, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- The first milk, colostrum, is an important source of nutrients and an exclusive source of immunoglobulins (Ig), essential for the growth and protection from infection of newborn pigs. Colostrum intake has also been shown to affect the vitality and behaviour of neonatal pigs. The objective of this study was to evaluate the effects of feeding colostrum and plasma immunoglobulin on brain development in neonatal pigs. Positive correlations were found between growth, levels of total protein and IgG in blood plasma and hippocampus development in sow-reared piglets during the first 3 postnatal days. In piglets fed an elemental diet (ED) for 24h, a reduced body weight, a lower plasma protein level and a decreased level of astrocyte specific protein in the hippocampus was observed, as compared to those that were sow-reared. The latter was coincident with a reduced microgliogenesis and an essentially diminished number of neurons in the CA1 area of the hippocampus after 72h. Supplementation of the ED with purified plasma Ig, improved the gliogenesis and supported the trophic and immune status of the hippocampus. The data obtained indicate that the development of the hippocampus structure is improved by colostrum or an Ig-supplemented elemental diet in order to stimulate brain protein synthesis and its development during the early postnatal period.
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| 23. |
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| 24. |
- Ranchhod, S. M., et al.
(författare)
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Potential neuroprotective strategies for perinatal infection and inflammation
- 2015
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 45, s. 44-54
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Tidskriftsartikel (refereegranskat)abstract
- Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in normal brain function and development, as well as being deleterious. Thus, treatment must achieve a delicate balance between possible beneficial and harmful effects. In this review, we discuss potential neuroprotective strategies targeting systemic infection or the resulting systemic and central inflammatory responses. We highlight the central importance of timing of treatment and the critical lack of studies of delayed treatment of infection/inflammation. (C) 2015 Elsevier Ltd. All rights reserved.
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| 25. |
- Rodrigues Meurer, Ywlliane da Silva, et al.
(författare)
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Postnatal exposure to fluoxetine led to cognitive-emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats
- 2021
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Ingår i: International Journal of Developmental Neuroscience. - : John Wiley & Sons. - 0736-5748 .- 1873-474X. ; 81:7, s. 616-632
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Tidskriftsartikel (refereegranskat)abstract
- The exposure to selective serotonin reuptake inhibitors (SSRIs) during development results in behavioural impairment in adulthood in humans and animal models. Indeed, serotonergic overexpression in early life leads to structural and functional changes in brain circuits that control cognition and emotion. However, the effects of developmental exposure to these substances on the behaviour of adolescent rats are conflicting and remain poorly characterised. We performed a behavioural screening to investigate the effects of postnatal exposure to fluoxetine on memory and behaviours related to anxiety, anhedonia, and depression, as well we evaluate the parvalbumin expression in hippocampus of juvenile (similar to PND45) female and male rats. Fluoxetine (daily 20 mg/kg s.c. injections from PND7-PND21)- or vehicle-treated adolescent rats went through several behavioural tasks (from PND 38 to PND52) and were subject to transcardial perfusion and brain removal for immunohistochemical analysis (PND53). We found that postnatal exposure to fluoxetine increased anxiety- and depression-like behaviours in the open field and sucrose preference and forced swimming tests, respectively. In addition, this treatment induced working memory and short-term (but not long-term) recognition memory impairments, and reduced parvalbumin-positive inter-neurons in the hippocampus. In addition, the results revealed developmental sex-dependent effects of fluoxetine postnatal treatment on adolescent rats' behaviour. These outcomes indicate that affective disorders and mnemonic alterations caused by SSRIs perinatal exposure can be present at adolescence.
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| 29. |
- Taylor, Linnéa, et al.
(författare)
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Scaffolding the retina: The interstitial extracellular matrix during rat retinal development.
- 2015
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 1873-474X .- 0736-5748. ; 42, s. 46-58
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the expression of interstitial extracellular matrix components and their role during retinal development. MATERIAL AND METHODS: Fibronectin (FN), collagen IV (Coll IV) and laminin 5 (Lam 5) expression in rat retinas from developmental stages E17 to adult were studied. In addition, PN5 full-thickness retinas were cultured for 7 days with dispase, which selectively cleaves FN and Coll IV, at either 0.5U/ml or 5.0U/ml for 3 or 24h. Eyecups and retinal cultures were examined morphologically using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Coll IV, Lam 5 and FN were all transiently expressed in the interstitial matrix of the retinal layers during development. The retinal layers in dispase treated explants was severely disturbed in a dose and time dependent manner. CONCLUSIONS: FN, Lam 5 and Coll IV, are present in the interstitial extracellular matrix during rat retinal development. Enzymatic cleavage of FN and Coll IV early in the lamination process disrupts the retinal layers implicating their pivotal role in this process.
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| 31. |
- Viberg, Henrik
(författare)
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Neonatal ontogeny and neurotoxic effect of decabrominated diphenyl ether (PBDE 209) on levels of synaptophysin and tau
- 2009
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Ingår i: International Journal of Developmental Neuroscience. - : Wiley. - 0736-5748 .- 1873-474X. ; 27:5, s. 423-429
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Tidskriftsartikel (refereegranskat)abstract
- Mice and rats have a period of rapid growth and development that occurs postnatally, while in humans the corresponding period is perinatal. This gives us the opportunity to study direct effects of chemicals during developmental processes of the central nervous system (CNS) in murine animals. Mammals have a marked period of rapid brain growth and development, the brain growth spurt (BGS), which is postnatal in mice and rats, spanning the first 3-4 weeks of life and reaching its peak around postnatal day 10. The proteins synaptophysin and tau are involved in developmental processes in the nervous system during the BGS in mice. One class of flame retardants, polybrominated diphenyl ethers (PBDEs), is present and increasing in the environment and in human milk, which is also true for the only congener still in use, decabrominated diphenyl ether (2,2',3,3',4,4',5,5',6,6'-decaBDE, PBDE 209). The present study was divided into two parts (a) the neonatal ontogeny of synaptophysin and tau and (b) the developmental neurotoxic effect of PBDE 209 on synaptophysin and tau during the neonatal ontogeny in mice. The level of synaptophysin measured on postnatal days 1, 3, 7, 10, 14, and 28, increased continuously during the neonatal period, while tau has a bell-shaped ontogeny curve that peaks between postnatal days 7 and 10. The effects of PBDE 209 on the developmental expression of synaptophysin and tau were examined in neonatal NMRI male mice, orally exposed on day 3 to 20.1mg PBDE 209/kg body weight. The animals were euthanized 7 days after exposure to PBDE 209 and levels of synaptophysin and tau were analyzed in the hippocampus and cerebral cortex. The protein analysis showed that synaptophysin had increased significantly in the hippocampus, but not in the cerebral cortex, in mice 7 days after exposure to PBDE 209. The analysis of protein levels showed no changes in tau in the hippocampus or cerebral cortex 7 days after exposure to PBDE 209 on postnatal day 3. A recent study shows that neonatal PBDE 209-exposure can affect levels of BDNF (brain-derived neurotrophic factor), CaMKII (Ca(2+)/calmodulin-dependent protein kinase II), and GAP-43 (growth associated protein 43), which are proteins that are important for normal brain development. The present study shows that PBDE 209 affects the level of synaptophysin in the developing brain, which further supports the recent findings that PBDE 209 can disturb components of normal brain maturation and act as a developmental neurotoxicological agent. Furthermore, this suggests that certain proteins involved in developmental processes can serve as markers of developmental neurotoxicity.
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