| 1. |
- Abbas, Abdul-Karim, 1959, et al.
(författare)
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S-sulfo-cysteine is an endogenous amino acid in neonatal rat brain but an unlikely mediator of cysteine neurotoxicity.
- 2008
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 33:2, s. 301-7
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Tidskriftsartikel (refereegranskat)abstract
- S-sulfo-cysteine (SSC) is an agonist of glutamate receptors which could be involved in cysteine-induced neurotoxicity. Here we analyzed SSC by HPLC and demonstrated that the concentration of SSC in cortex of cysteine-injected rats increased to 1.4 microM, about four times the value of control rats. The neurotoxic effect of SSC was evaluated in slice cultures of rat hippocampus and compared to NMDA and cysteine. The neurotoxicity threshold of SSC was well above the tissue concentration. Our results show that SSC increases in neonatal rat brain after cysteine injection but reaches a tissue concentration far below concentrations that induce neurotoxicity in vitro. Thus, even if all the tissue SSC after cysteine injection was extracellular it would be below the threshold for toxicity, indicating that SSC is not a main excitotoxin involved in cysteine toxicity.
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| 2. |
- Andersson, Anna, et al.
(författare)
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Lactate contributes to ammonia-mediated astroglial dysfunction during hyperammonemia.
- 2009
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 34:3, s. 556-65
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Tidskriftsartikel (refereegranskat)abstract
- Even though ammonia is considered to underlie nervous system symptoms of dysfunction during hyperammonemia, lactate, which increases as a metabolic consequence of high ammonia levels, might also be a contributing factor. The data presented here show that NH4Cl (5 mM) mediates astroglial cell swelling, and that treatment with NH4Cl or lactate (25 mM) causes rearrangements of actin filaments and reduces astroglial glutamate uptake capacity. Co-application with BaCl2, which blocks astroglial uptake of NH4+, prevents NH4Cl-mediated cell swelling and rearrangement of actin filaments, but does not reduce NH4Cl-induced glutamate uptake capacity inhibition. Neither NH4Cl nor lactate affected glutamate uptake or protein expression in microglial cultures, indicating that astroglial cells are more susceptible to the neurotoxic affects of ammonia. Our results suggest that ammonium underlies brain edema, but that lactate can contribute to some of the cellular dysfunctions associated with elevated cerebral levels of ammonia.
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| 3. |
- Archer, Trevor, 1949, et al.
(författare)
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Functional consequences of iron overload in catecholaminergic interactions: the Youdim factor
- 2007
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Ingår i: Neurochemical Research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 32:10, s. 1625-1639
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Forskningsöversikt (refereegranskat)abstract
- The influence of postnatal iron overload upon implications of the functional and interactive role of dopaminergic and noradrenergic pathways that contribute to the expressions of movement disorder and psychotic behaviours in mice was studied in a series of experiments. (1) Postnatal iron overload at doses of 7.5 mg/kg (administered on Days 10–12 post partum) and above, invariably induced a behavioural syndrome consisting of an initial (1st 20–40 min of a 60-min test session) hypoactivity followed by a later (final 20 min of a 60-min test session) hyperactivity, when the mice were tested at adult ages (age 60 days or more). (2) Following postnatal iron overload, subchronic treatment with the neuroleptic compounds, clozapine and haloperidol, dose-dependently reversed the initial hypoactivity and later hyperactivity induced by the metal. Furthermore, DA D2 receptor supersensitivity (as assessed using the apomorphine-induced behaviour test) was directly and positively correlated with iron concentrations in the basal ganglia. (3) Brain noradrenaline (NA) denervation, using the selective NA neurotoxin, DSP4, prior to administration of the selective DA neurotoxin, MPTP, exacerbated both the functional (hypokinesia) and neurochemical (DA depletion) effects of the latter neurotoxin. Treatment with L-Dopa restored motor activity only in the animals that had not undergone NA denervation. These findings suggest an essential neonatal iron overload, termed “the Youdim factor”, directing a DA–NA interactive component in co-morbid disorders of nigrostriatal-limbic brain regions.
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| 4. |
- Augestad, Ingrid Lovise, et al.
(författare)
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Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat
- 2017
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Ingår i: Neurochemical Research. - : SPRINGER/PLENUM PUBLISHERS. - 0364-3190 .- 1573-6903. ; 42:6, s. 1599-1609
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Tidskriftsartikel (refereegranskat)abstract
- Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.
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| 5. |
- Björklund, Ulrika, 1970, et al.
(författare)
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Primary cultures from cerebral cortex and hippocampus enriched in glutamatergic and GABAergic neurons.
- 2010
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Ingår i: Neurochemical research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 35:11, s. 1733-42
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to define a primary culture system enriched in neurons using a defined culture medium, and characterize the model system as to cellular morphology and neuronal phenotypes. We found that these primary neuron enriched cultures from either newborn rat cerebral cortex or hippocampus contain small GABAergic and large glutamatergic neurons as well as astrocytes and microglia. Astrocytes in these cultures are morphologically differentiated with long, slender processes and interact with soluble factors responsible for induction and expression of the glutamate transporter GLT-1. The cultures achieve the highest expression of the vesicular glutamate transporter 1 (VGLUT1) and GLT-1 after 20 days in vitro. Conditioned media from these neuron enriched cultures also induced GLT-1 expression in primary astrocytic cultures, which were free from neurons. The amount of glutamatergic neurons guides the morphological maturation of astrocytes and GLT-1 expression both in the neuron enriched cultures and in the conditioned media supplemented astrocytic cultures. Interestingly, these cultures were not influenced or activated by the inflammatory stimulus lipopolysaccharide. This suggests that soluble factors from neurons protect microglia and astrocytes to become inflammatory reactive. In conclusion we have developed a well characterized culture model system enriched in neurons, taken from newborn rats and cultured in defined media. The neurons express different neuronal phenotypes. Such a model system is valuable when studying interactions between neurons and glial cells.
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| 6. |
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| 7. |
- Campo, Chiara, et al.
(författare)
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Genetic Susceptibility to Bortezomib-Induced Peripheral Neuroropathy : Replication of the Reported Candidate Susceptibility Loci
- 2017
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Ingår i: Neurochemical Research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 42:3, s. 925-931
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of proteasome inhibitors in the treatment of multiple myeloma (MM) patients has been a therapeutic success. Peripheral neuropathy (PNP) remains one of the most frequent side-effects experienced by patients who receive these novel agents. Recent investigations on the mechanisms of PNP in patients treated with bortezomib have suggested genetic susceptibility to neurotoxicity. We used data from a genome-wide association study conducted on 646 bortezomib-treated German MM patients to replicate the previously reported associations between single-nucleotide polymorphisms (SNPs) in candidate genes and PNP in MM patients, including 298 SNPs with a nominal significance (p value <0.05). Twelve associations were confirmed at a significance level p value <0.05. The corresponding SNPs are located in genes involved in drug metabolism (ABCC1, ABCC6), development and function of the nervous system (POGZ, NFAT pathway, EDN1), modulation of immune responses (IL17RD, IL10RA) and the NF-κB signaling pathway (PSMB4, BTCR, F2). We systematically investigated functional consequences of those variants using several bioinformatics tools, such as HaploRegV4.1, RegulomeDB and UCSC Genome Browser. Expression quantitative trait loci (eQTL) data suggested that some of the identified SNPs might influence gene expression through a differential recruitment of transcription factors. In conclusion, we confirmed some of the recently reported associations between germline variation and PNP. Elucidating the mechanisms underlying these associations will contribute to the development of new strategies for the prevention or reduction of PNP.
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| 8. |
- Correa, Fernando, et al.
(författare)
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Dual TNF alpha-Induced Effects on NRF2 Mediated Antioxidant Defence in Astrocyte-Rich Cultures: Role of Protein Kinase Activation
- 2012
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Ingår i: Neurochemical Research. - : Springer Science and Business Media LLC. - 0364-3190 .- 1573-6903. ; 37:12, s. 2842-2855
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor-alpha (TNF alpha) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNF alpha on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, gamma glutamylcysteine ligase (gamma GCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of gamma GCL (gamma GCL-C and gamma GCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNF alpha. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNF alpha increased GSH, gamma GCL activity, the protein levels of gamma GCL-M, gamma GCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3 beta further enhanced transcription. In contrast treatment with TNF alpha for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNF alpha. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3 beta, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNF alpha (24 h treatment) protected the cells from oxidative stress through elevated gamma GCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer's disease, the effect of TNF alpha is detrimental.
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