排序方式: 共有24条查询结果,搜索用时 15 毫秒
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Tobias Wächter Sebastian Röhrich Anita Frank Katiuska Molina-Luna Ana Pekanovic Benjamin Hertler Maximilan Schubring-Giese Andreas R. Luft 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2010,200(3-4):319-323
Functional imaging studies in humans and electrophysiological data in animals suggest that corticostriatal circuits undergo plastic modifications during motor skill learning. In motor cortex and hippocampus circuit plasticity can be prevented by protein synthesis inhibition (PSI) which can interfere with certain forms learning. Here, the hypothesis was tested that inducing PSI in the dorsal striatum by bilateral intrastriatal injection of anisomycin (ANI) in rats interferes with learning a precision forelimb reaching task. Injecting ANI shortly after training on days 1 and 2 during 4 days of daily practice (n = 14) led to a significant impairment of motor skill learning as compared with vehicle-injected controls (n = 15, P = 0.033). ANI did not affect the animals’ motivation as measured by intertrial latencies. Also, ANI did not affect reaching performance once learning was completed and performance reached a plateau. These findings demonstrate that PSI in the dorsal striatum after training impairs the acquisition of a novel motor skill. The results support the notion that plasticity in basal ganglia circuits, mediated by protein synthesis, contributes to motor skill learning. 相似文献
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Molina-Luna K Buitrago MM Hertler B Schubring M Haiss F Nisch W Schulz JB Luft AR 《Journal of neuroscience methods》2007,161(1):118-125
Stimulation mapping of motor cortex is an important tool for assessing motor cortex physiology. Existing techniques include intracortical microstimulation (ICMS) which has high spatial resolution but damages cortical integrity by needle penetrations, and transcranial stimulation which is non-invasive but lacks focality and spatial resolution. A minimally invasive epidural microstimulation (EMS) technique using chronically implanted polyimide-based thin-film microelectrode arrays (72 contacts) was tested in rat motor cortex and compared to ICMS within individual animals. Results demonstrate reliable mapping with high reproducibility and validity with respect to ICMS. No histological evidence of cortical damage and the absence of motor deficits as determined by performance of a motor skill reaching task, demonstrate the safety of the method. EMS is specifically suitable for experiments integrating electrophysiology with behavioral and molecular biology techniques. 相似文献
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Edgardo Rodríguez-Lebrón Maria doCarmo Costa Katiuska Luna-Cancalon Therese M Peron Svetlana Fischer Ryan L Boudreau Beverly L Davidson Henry L Paulson 《Molecular therapy》2013,21(10):1909-1918
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease caused by a polyglutamine expansion in the deubiquitinating enzyme, Ataxin-3. Currently, there are no effective treatments for this fatal disorder but studies support the hypothesis that reducing mutant Ataxin-3 protein levels might reverse or halt the progression of disease in SCA3. Here, we sought to modulate ATXN3 expression in vivo using RNA interference. We developed artificial microRNA mimics targeting the 3′-untranslated region (3′UTR) of human ATXN3 and then used recombinant adeno-associated virus to deliver them to the cerebellum of transgenic mice expressing the full human disease gene (SCA3/MJD84.2 mice). Anti-ATXN3 microRNA mimics effectively suppressed human ATXN3 expression in SCA3/MJD84.2 mice. Short-term treatment cleared the abnormal nuclear accumulation of mutant Ataxin-3 throughout the transduced SCA3/MJD84.2 cerebellum. Analysis also revealed changes in the steady-state levels of specific microRNAs in the cerebellum of SCA3/MJD84.2 mice, a previously uncharacterized molecular phenotype of SCA3 that appears to be dependent on mutant Ataxin-3 expression. Our findings support the preclinical development of molecular therapies aimed at halting the expression of ATXN3 as a viable approach to SCA3 and point to microRNA deregulation as a potential surrogate marker of SCA3 pathogenesis. 相似文献
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Mitnick CD Shin SS Seung KJ Rich ML Atwood SS Furin JJ Fitzmaurice GM Alcantara Viru FA Appleton SC Bayona JN Bonilla CA Chalco K Choi S Franke MF Fraser HS Guerra D Hurtado RM Jazayeri D Joseph K Llaro K Mestanza L Mukherjee JS Muñoz M Palacios E Sanchez E Sloutsky A Becerra MC 《The New England journal of medicine》2008,359(6):563-574
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Andrea Lynne Cheville Jeffrey Rogers Basford Katiuska Dos Santos Kurt Kroenke 《Archives of physical medicine and rehabilitation》2014
Objective
To assess the influence of symptom intensity, mood, and comorbidities on patient-clinician agreement and the consistency of responses to functional patient-reported outcomes (PROs).Design
Two data sources were used. The first, a cross-sectional database of patients with breast cancer who completed functional PROs and were administered the FIM, was used to examine whether average pain intensity (as measured with an 11-point numeric rating scale [NRS]) and Rand Mental Health inventory scores differed among those rating their functional independence as different than clinicians. The second, a longitudinal database of 311 adults with late-stage lung cancer who completed the Activity Measure for Post Acute Care Computer Adaptive Test (AM PAC CAT) with differences between their expected and actual responses as reflected in their AM PAC CAT SEs.Setting
Two tertiary medical centers.Participants
Data source #1, 163 women with stage IV breast cancer; data source #2, 311 adults with late-stage lung cancer.Interventions
Not applicable.Main Outcome Measures
Data source #1, FIM, pain NRS, Older Americans Resource Study activities of daily living subscale, Physical Function-10, Mental Health Inventory-17. Data source #2, AM PAC CAT and NRS symptom ratings.Results
Pain intensity was significantly higher when clinicians and patients disagreed regarding a patient's independence in the ability to transfer (NRS pain severity, 3.78 vs 2.40; P=.014), groom (3.71 vs 2.36, P=.009), bathe (3.76 vs 2.40, P=.016), and dress (3.09 vs 2.44, P=.034). The magnitude of AM PAC CAT SEs was significantly associated with the severity of participants' pain, dyspnea, and fatigue, as well as the presence of musculoskeletal disorders and coronary artery disease. Neither mood nor emotional distress was associated with clinician-patient agreement or AM PAC CAT SE.Conclusions
Pain intensity is associated with disagreement between patients and clinicians about the patient's level of functioning. Moreover, physical symptoms (pain, dyspnea, fatigue) as well as specific medical comorbidities (musculoskeletal disorders, coronary artery disease), but not mood, are associated with inconsistency in patients' assessment of their functional abilities. 相似文献10.
Schubring-Giese M Molina-Luna K Hertler B Buitrago MM Hanley DF Luft AR 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2007,181(2):359-365
Many motor rehabilitation therapies are based on principles of motor learning. Motor learning depends on preliminary knowledge
of the trained and other (similar) skills. This study sought to investigate the influence of prior skill knowledge on re-learning
of a precision reaching skill after a cortical lesion in rat. One group of animals recovered a previously known skill (skill
training, followed by stroke and re-learning training, TST, n = 8). A second group learned the skill for the first time after stroke (ST, n = 6). A control group received prolonged training without stroke (n = 6). Unilateral partial motor cortex lesions were induced photothrombotically after identifying the forelimb representation
using epidural stimulation mapping. In TST animals, re-learning after stroke was slower than learning before stroke (post
hoc repeated measures ANOVA P = 0.039) and learning in the control group (P = 0.033). De novo learning after stroke (ST group) was not different from healthy learning. These findings show that skill
learning can be performed if the motor cortex is partially lesioned; re-learning of a skill after stroke is slowed by prior
knowledge of the skill. It remains to be tested in humans whether task novelty positively influences rehabilitation therapy. 相似文献