ارتباط رفتاری و عصب فیزیولوژیک تخلیه دوپامین انشعابات جسم مخطط: مدل جوندگان بیماری پارکینسون
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|31108||2011||8 صفحه PDF||سفارش دهید||4788 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Journal of Communication Disorders, Volume 44, Issue 5, September–October 2011, Pages 549–556
Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and cranial motor impairments in PD may differ. Animal models provide a mechanism by which the potential neural dysfunctions underlying these different motor impairments may be characterized. Central goals to our laboratory have been to (a) determine the differential responses of cranial motor and limb motor function to striatal dopamine depletion and (b) determine the differential effects of striatal dopamine depletion on the integrity of cranial motor and limb motor neural circuits. This paper details the use of a comprehensive battery of limb and cranial motor behavioral tasks and the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits in a rodent model of PD. Our work suggests that striatal dopamine depletion does differentially affect cranial and limb motor function and corticospinal and corticobulbar circuits. Further, we propose that cranial motor impairments in PD may be mediated by pathology both within and outside nigrostriatal dopamine system. Learning outcomes: Readers will be able to (a) describe a set of motor tests used to assess limb motor and cranial motor function in an animal model of Parkinson's disease, (b) understand the application of intracortical microstimulation to assess corticospinal and corticobulbar circuits, (c) describe the differential effects of dopamine depletion on limb motor and cranial motor function in a rodent model of PD, and (d) understand the potential role of dysfunction outside the nigrostriatal system mediating cranial motor impairments in Parkinson's disease.
Parkinson's disease (PD) is a chronic, progressive and currently non-curable neurodegenerative disease associated with substantial morbidity, increased mortality, and high economic burden. Approximately 1.5 million Americans are currently diagnosed with PD at a cost of $23 billion dollars annually (Weintraub, Comella, & Horn, 2008) with a three to four fold increase in disease rate expected to occur over the next ten years (Tanner & Ben-Shlomo, 1999). Although PD is classically defined by the presence of general motor symptoms that include resting tremor, bradykinesia, rigidity, and postural instability, cranial motor deficits in the form of a hypokinetic dysarthria and dysphagia are reported to occur in 90% of PD patients (Sapir, Ramig, & Fox, 2008). These impairments have been documented to be associated with significant reductions in quality of life, social interactions and mental well-being (Plowman-Prine, Sapienza, et al., 2009). Alarmingly, aspiration pneumonia constitutes the leading cause of death in PD, resulting in a life expectancy ten years below the general population (Hely, Reid, Adena, Halliday, & Morris, 2008). Speech and voice subsystems significantly affected in PD may include respiration, phonation, articulation, resonance, and prosody (Schulz & Grant, 2000). Hallmark perceptual characteristics of Parkinsonian speech include reduced loudness, monotony of pitch and loudness, reduced stress, variable rate, short rushes of speech, imprecise consonants, and a harsh and breathy voice (Darley et al., 1969, Plowman-Prine et al., 2009a and Ramig et al., 2008). Swallowing impairments in PD are usually attributed to movement dysfunction of affected bulbar structures and include: lingual tremor, repetitive lingual pumping, anterior bolus leakage, slow or impaired mastication, mandible rigidity, reduced and delayed pharyngeal constrictor contraction, slow and reduced laryngeal excursion, slowing of true vocal fold closure, reduced epiglottic range of movement, reduced and delayed opening of the esophageal sphincter's, abnormal esophageal motility, and esophageal bolus redirection (Chou et al., 2007, Durham et al., 1993, Leopold and Kagel, 1996, Leopold and Kagel, 1997 and Nagaya et al., 1998). These bulbar movement abnormalities may contribute to functional swallowing deficits that include: poor oral bolus control, ineffective oral transit, increased oral transit time, oral buccal residue, premature spillage of the bolus into the valleculae, delay in the execution of the swallow reflex, stasis in the valleculae or pyriforms, penetration and/or aspiration, and gastroesophageal reflux (Pitts et al., 2008, Troche et al., 2008, Troche et al., 2010a and Troche et al., 2010b).
نتیجه گیری انگلیسی
Parkinson's disease significantly impairs cranial motor function and while current medical interventions alleviate general motor dysfunction, they fail to consistently benefit cranial motor impairments in this disease population. This paper has detailed the use of a rodent model to investigate the potential different neuropathologies mediating cranial motor vs. limb motor dysfunction in PD. Our work demonstrates that (a) striatal dopamine depletion significantly impairs both limb and cranial motor function and this is reflected as a loss in cortical moment representations and (b) limb motor impairments are more severe than cranial motor impairments, are related to degree of dopamine depletion, and are associated with a more dramatic loss in movement representations. These results suggests that limb motor function and circuits are more sensitive to dopamine transmission and that cranial motor function may be due to dysfunction within other neurotransmitter systems and structures in PD. Future work will explore this possibility and use this model as a platform to develop and test neurobiologically based therapies for cranial motor function in PD.