Olfaction in Parkinson's disease and related disorders

被引:317
作者
Doty, Richard L. [1 ]
机构
[1] Univ Penn, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Ctr Smell & Taste, Philadelphia, PA 19104 USA
关键词
Parkinson's disease; Neurodegenerative diseases; Olfaction; Genetics; Lewy body disease; Aging; Dopamine; Acetylcholine; Norepinephrine; Serotonin; Psychophysics; Electrophysiology; Functional imaging; Dystonia; MULTIPLE SYSTEM ATROPHY; PROGRESSIVE SUPRANUCLEAR PALSY; AMYOTROPHIC-LATERAL-SCLEROSIS; SMELL IDENTIFICATION TEST; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE RAT MODEL; NIGROSTRIATAL DOPAMINERGIC DENERVATION; PRIMATE ORBITOFRONTAL CORTEX; ODOR DETECTION PERFORMANCE; DRUG-INDUCED PARKINSONISM; G2019S MUTATION CARRIERS;
D O I
10.1016/j.nbd.2011.10.026
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of et-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:527 / 552
页数:26
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