| 1. |
- Abbas, Abdul-Karim, 1959
(author)
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Evidence for constitutive protein synthesis in hippocampal LTP stabilization
- 2013
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In: Neuroscience. - : Elsevier BV. - 0306-4522. ; 246, s. 301-311
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Journal article (peer-reviewed)abstract
- The notion that blockade of constitutive protein synthesis underlies the effect of protein synthesis inhibitors (PSIs) on long-term potentiation (LTP) stabilization was examined using the rat hippocampal CA3-CA1 synapse. Using a biochemical assay we found protein synthesis rate largely recovered 1h after wash-out of cycloheximide (CHX). Nonetheless, a 4-h CHX application followed by wash-out 1h prior to LTP resulted in a significant decrement of LTP stabilization. Wash-out initiated just prior to LTP, thus extending protein synthesis inhibition well into the post-LTP period, resulted in no further effect on LTP. However, short pre- and continuous post-tetanization application of PSIs failed to influence LTP persistence for up to 7h. Addition of hydrogen peroxide (H2O2) 5-25min following LTP induction resulted in parallel depression of potentiated and non-potentiated inputs, leaving LTP seemingly unaltered. However, in the presence of cyxloheximide the H2O2 application resulted in a significant reduction of LTP. In conclusion: LTP stabilization was impaired by pre-LTP application of protein synthesis inhibition but not by post-LTP application unless the slices were exposed to oxidative stress. We submit that these results favor the notion that constitutive rather than triggered protein synthesis is important for LTP stabilization.
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| 2. |
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| 3. |
- Alsiö, Johan, et al.
(author)
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Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats
- 2010
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In: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 171:3, s. 779-787
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Journal article (peer-reviewed)abstract
- The nucleus accumbens (NAcc) mediates feeding reward; its activity reflects tastants' hedonic value. NAcc dopamine guides immediate responses to reward, however, its involvement in establishing long-term responses after a period of exposure to palatable foods has not been defined. Furthermore, reward-driven overeating propels weight increase, but the scale of weight gain depends on animals' obesity-prone (OP) or -resistant (OR) phenotype. It is unclear whether the NAcc dopamine response to palatable food depends on obesity susceptibility. We investigated the effect of unrestricted extended access to high-fat high-sugar (HFHS) diet on expression of genes encoding dopamine receptors in the NAcc of OP and OR rats. We examined persistence of HFHS diet-induced changes in D(1) and D(2) gene expression in OP and OR rats subjected to HFHS withdrawal (bland chow for 18 days). Effects of restricted access to HFHS by pair-feeding were also studied. Using reverse transcriptase PCR (RT-PCR), we found that NAcc D(1) mRNA was downregulated after long-term HFHS access in OP vs. OR animals. The effect was also observed after 18 days of HFHS withdrawal. Furthermore, restricted HFHS led to downregulation of D(1) as well as of D(2) mRNA levels compared to chow-fed controls. A difference in the expression of mu opioid receptor in the NAcc was also detected between the OP and OR rats during access to palatable food but not after withdrawal. We conclude that exposure to HFHS diets has lasting consequences for the NAcc dopamine system, perhaps modifying the motivation to search for food reward. The fact that the NAcc D(1) expression changes in OP animals after long-term exposure to palatable food and that this effect extends well into the reward discontinuation phase, implicates the D(1) receptor in the propensity to overeat and, in effect, gain weight in obesity prone individuals.
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| 4. |
- Alvarez, S., et al.
(author)
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PERIPHERAL MOTOR AXONS OF SOD1(G127X) MUTANT MICE ARE SUSCEPTIBLE TO ACTIVITY-DEPENDENT DEGENERATION
- 2013
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In: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 241, s. 239-249
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Journal article (peer-reviewed)abstract
- Motor neuron disorders may be associated with mitochondrial dysfunction, and repetitive electrical impulse conduction during energy restriction has been found to cause neuronal degeneration. The aim of this study was to investigate the vulnerability of motor axons of a presymptomatic late-onset, fast-progression SOD1(G127x) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle action potentials and ascending compound nerve action potentials were recorded from plantar muscles and from the sciatic nerve, respectively. Repetitive stimulation (RS) was carried out in interrupted trains of 200-Hz for 3 h. During the stimulation-sequence there was progressive conduction failure in WT and, to a lesser extent, in the SOD1(G127x). By contrast, 3 days after RS the electrophysiological responses remained reduced in the SOD1(G127x) but recovered completely in WT. Additionally, morphological studies showed Wallerian degeneration in the disease model. Nerve excitability testing by "threshold-tracking" showed that axons recovering from RS had changes in excitability suggestive of membrane hyperpolarization, which was smaller in the SOD1(G127x) than in WT. Our data provide proof-of-principle that SOD1(G127x) axons are less resistant to activity-induced changes in ion-concentrations. It is possible that in SOD1(G127x) there is inadequate energy-dependent Na+/K+ pumping, which may lead to a lethal Na+ overload. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 5. |
- Bannatyne, B A, et al.
(author)
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Inhibitory inputs to four types of spinocerebellar tract neurons in the cat spinal cord.
- 2012
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 226, s. 253-69
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Journal article (peer-reviewed)abstract
- Spinocerebellar tract neurons are inhibited by various sources of input via pathways activated by descending tracts as well as peripheral afferents. Inhibition may be used to modulate transmission of excitatory information forwarded to the cerebellum. However it may also provide information on the degree of inhibition of motoneurons and on the operation of inhibitory premotor neurons. Our aim was to extend previous comparisons of morphological substrates of excitation of spinocerebellar neurons to inhibitory input. Contacts formed by inhibitory axon terminals were characterised as either GABAergic, glycinergic or both GABAergic/glycinergic by using antibodies against vesicular GABA transporter, glutamic acid decarboxylase and gephyrin. Quantitative analysis revealed the presence of much higher proportions of inhibitory contacts when compared with excitatory contacts on spinal border (SB) neurons. However similar proportions of inhibitory and excitatory contacts were associated with ventral spinocerebellar tract (VSCT) and dorsal spinocerebellar tract neurons located in Clarke's column (ccDSCT) and the dorsal horn (dhDSCT). In all of the cells, the majority of inhibitory terminals were glycinergic. The density of contacts was higher on somata and proximal versus distal dendrites of SB and VSCT neurons but more evenly distributed in ccDSCT and dhDSCT neurons. Variations in the density and distribution of inhibitory contacts found in this study may reflect differences in information on inhibitory processes forwarded by subtypes of spinocerebellar tract neurons to the cerebellum.
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| 6. |
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| 7. |
- Barkholt, P., et al.
(author)
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Long-term polarization of microglia upon α-synuclein overexpression in nonhuman primates
- 2012
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 208, s. 85-96
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Journal article (peer-reviewed)abstract
- We have previously shown that persistent a-synuclein overexpression in ventral midbrain of marmoset leads to a distinctive neurodegenerative process and motor defects. The neurodegeneration was confined to caudate putamen dopaminergic fibers in animals overexpressing wild-type (wt) alpha-synuclein. However, A53T alpha-synuclein overexpression induced neurodegeneration that resulted in nigral dopaminergic cell death. Here, we analyze the microglia population in the midbrain of these animals by stereological quantification of lba1 + cells. Our data here show that monkeys overexpressing A53T alpha-synuclein showed a long-term increase in microglia presenting macrophagic morphology. However, wt alpha-synuclein overexpression, despite the absence of dopaminergic cell death, resulted in a permanent robust increase of the microglia population characterized by a range of distinct morphological types that persisted after 1 year. These results confirm that the microglial response differs depending on the type of alpha-synuclein (wt/A53T) and/or whether alpha-synuclein expression results in cell death or not, suggesting that microglia may play different roles during disease progression. Furthermore, the microglial response is modulated by events related to alpha-synuclein expression in substantia nigra and persists in the long term. The data presented here is in agreement with that previously observed in a recombinant adeno-associated virus (rAAV) alpha-synuclein rat model, thereby validating both the findings and the model, and highlighting the translational potential of the rodent model to higher species closer to humans. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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| 8. |
- Berg, L K, et al.
(author)
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Pre- and postsynaptic localization of NMDA receptor subunits at hippocampal mossy fibre synapses.
- 2013
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In: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 230, s. 139-150
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Journal article (peer-reviewed)abstract
- The N-methyl-D-aspartate (NMDA) type of glutamate receptors is involved in synaptic plasticity in hippocampal mossy fibre-CA3 pyramidal neuron synapses. The ultrastructural localization of NMDA receptor subunits at this synapse type is not known. By postembedding electron microscopic immunogold cytochemistry we show that the NMDA receptor subunits GluN1, GluN2A, GluN2B, GluN2C and GluN2D are located in postsynaptic membranes of mossy fibre as well as CA3 recurrent associational commissural synapses. In the mossy fibres the GluN1, GluN2B and GluN2D labelling patterns suggested that these subunits were located also presynaptically in nerve terminal membranes and in mossy fibre axons. GluN3B was predominantly present in mossy fibre synapses as compared to recurrent associational commissural synapses, showing a presynaptic labelling pattern. In conclusion, while the postsynaptic localization of GluN1, GluN2A, GluN2B, and GluN2D is in good agreement with the recent finding of NMDA receptor-dependent long term potentiation (LTP) at CA3 mossy fibre synapses, we propose that presynaptic GluN1, GluN2B, GluN2D and GluN3B subunits could be involved in plastic phenomena such as certain types of LTP and recurrent mossy fibre growth.
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| 9. |
- Block, Linda, et al.
(author)
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A new concept affecting restoration of inflammation-reactive astrocytes.
- 2013
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 250, s. 536-45
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Journal article (peer-reviewed)abstract
- Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.
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| 10. |
- Block, Linda, et al.
(author)
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Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2+) signaling in lipopolysaccharide pretreated astrocytes.
- 2012
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 205, s. 1-9
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Journal article (peer-reviewed)abstract
- Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca(2+) responses. EM-1 stimulated the μ-opioid receptor from 10(-15) M up to 10(-4) M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca(2+) responses. However, a combination of ultralow concentration naloxone (10(-12) M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca(2+) responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca(2+) transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca(2+) transients were oscillated. To restore the EM-1-evoked Ca(2+) transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca(2+) transients.
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