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- Engblom, David, et al.
(författare)
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Glutamate receptors on dopamine neurons control the persistence of cocaine seeking
- 2008
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Ingår i: Neuron. - : Elsevier Science B.V., Amsterdam.. - 0896-6273 .- 1097-4199. ; 59:3, s. 497-508
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking behavior.
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| 2. |
- Gallo, Valentina, et al.
(författare)
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Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
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Ingår i: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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| 3. |
- Mameli, Manuel, et al.
(författare)
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Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc
- 2009
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 12:8, s. 1036-U108
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Tidskriftsartikel (refereegranskat)abstract
- Addictive drugs hijack mechanisms of learning and memory that normally underlie reinforcement of natural rewards and induce synaptic plasticity of glutamatergic transmission in the mesolimbic dopamine (DA) system. In the ventral tegmental area (VTA), a single exposure to cocaine efficiently triggers NMDA receptor-dependent synaptic plasticity in DA neurons, whereas plasticity in the nucleus accumbens (NAc) occurs only after repeated injections. Whether these two forms of plasticity are independent or hierarchically organized remains unknown. We combined ex vivo electrophysiology in acute brain slices with behavioral assays modeling drug relapse in mice and found that the duration of the cocaine-evoked synaptic plasticity in the VTA is gated by mGluR1. Overriding mGluR1 in vivo made the potentiation in the VTA persistent. This led to synaptic plasticity in the NAc, which contributes to cocaine-seeking behavior after protracted withdrawal. Impaired mGluR1 function in vulnerable individuals could represent a first step in the recruitment of the neuronal network that underlies drug addiction.
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| 4. |
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| 5. |
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| 6. |
- Rodriguez, Jose F., et al.
(författare)
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The Effect of Material Model Formulation in the Stress Analysis of Abdominal Aortic Aneurysms
- 2009
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 37:11, s. 2218-2221
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Tidskriftsartikel (refereegranskat)abstract
- A reliable estimation of wall stress in Abdominal Aortic Aneurysms (AAAs), requires performing an accurate three-dimensional reconstruction of the medical image-based native geometry and modeling an appropriate constitutive law for the aneurysmal tissue material characterization. A recent study on the biaxial mechanical behavior of human AAA tissue specimens demonstrates that aneurysmal tissue behaves mechanically anisotropic. Results shown in this communication show that the peak wall stress is highly sensitive to the anisotropic model used for the stress analysis. In addition, the present investigation indicates that structural parameters (e.g., collagen fiber orientation) should be determined independently and not by means of non-linear fitting to stress-strain test data. Fiber orientation identified in this manner could lead to overestimated peak wall stresses.
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| 7. |
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| 8. |
- Yam-Puc, Alejandro, et al.
(författare)
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Trinorsesquiterpenoids from the Root Extract of Pentalinon andrieuxii
- 2009
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 72:4, s. 745-748
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Tidskriftsartikel (refereegranskat)abstract
- Two unusual trinorsesquiterpenoids, urechitols A (1) and B (2), were isolated from the root extract of Pentalinon andrieuxii, a plant used commonly in Yucatecan traditional medicine to treat leishmaniasis. The structures of I and 2 were identified by interpretation of their spectroscopic data and chemical correlation reactions. The relative stereochemistry of I was confirmed through an X-ray crystallographic study.
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