帕金森病与嗅觉障碍

帕金森病被认为是纯运动性疾病,近年来,越来越多的研究发现帕金森病患者存在感觉障碍,尤其是嗅觉障碍。帕金森病患者可出现嗅觉阀值增高,嗅觉辨别能力下降,嗅觉诱发电位潜伏期延长。嗅球、海马等部位神经元的破坏可能是导致嗅觉障碍的原因。嗅觉障碍的发生可能与遗传因素、病毒感染、环境因素或神经递质的改变有关。     

嗅觉障碍与阿尔茨海默病的研究进展

阿尔茨海默病(Alzheimer’s disease,AD)患者嗅觉系统病理改变与皮层退行性变的损害程度完全一致,而且嗅觉系统发生病变在时间上早于皮层病变。AD患者均有不同程度的嗅觉缺损,表现为嗅觉阈升高,嗅觉识别和嗅觉记忆减退。嗅觉缺损可见于AD的前期。是AD早期诊断的重要指标。嗅觉系统与大脑皮层许多部位有广泛联系,药物经嗅觉通路能被转运到脑内多个部位,通过嗅觉通路有可能找到治疗AD有效药物。     

嗅觉障碍与阿尔茨海默病

阿尔茨海默病（AD）为老年期常见的退行性神经变性疾病,以进行性记忆力、智力和认知功能减退为主要表现,至今病因未明,现有药物仅对疾病早期有效,因此,早诊断、早治疗意义重大。阿尔茨海默病的典型病理改变最先累及内嗅区皮质（EC）,然后逐渐向海马等扩散,最终累及全脑皮质。     

嗅觉障碍与阿尔茨海默病

阿尔茨海默病(AD)为老年期常见的退行性神经变性疾病,以进行性记忆力、智力和认知功能减退为主要表现,至今病因未明,现有药物仅对疾病早期有效,因此,早诊断、早治疗意义重大.     

帕金森病患者嗅觉障碍与嗅觉相关脑区结构变化关系的研究

目的利用基于体素的形态学分析（VBM）研究原发性帕金森病患者嗅觉相关脑区结构改变及其与嗅觉障碍之间的关系,探讨其作为早期诊断的可能性。方法应用“五味嗅觉测试液”对26例诊断明确的早期原发性帕金森病患者进行嗅觉功能检测,并与年龄、病程和病情严重程度[帕金森病统一评价量表（UPDRS）]进行相关分析。磁化准备快速梯度回波序列获取三维结构图像,SPM5软件后处理,通过配准、分割获得白质密度图像,经调试获得白质体积图像。结果帕金森病组患者嗅觉察觉阈值和嗅觉识别阈值分别为0．66±0．84和2．41±0．74,显著高于对照组的-0．64±0．83和1．08±0．54（Z=4．455,P=0．000;t=4．898,P=0．000）。帕金森病组患者嗅觉功能与年龄（察觉阈值：n=0．199,P=0．330;识别阈值：n=0．256,P=0．207）、病程（察觉阈值：n=0．123,P=0．550;识别阈值：n=0．055,P=0．789）及UPDRSⅢ评分（察觉阈值：n=0．229,P=0．260;识别阈值：rs=0．379,P=0．056）无明显相关性;UPDRS总评分与嗅觉察觉阈值无相关性（rs=0．314,P=0．118）,但与嗅觉识别阈值呈正相关（n=0．397,P=0．045）。与对照组相比,原发性帕金森病组患者右侧枕叶（BA17～19区）、左侧扣带回后部（BA23,30,31区）、左侧枕叶（BA18,19区）和左侧中央旁小叶（BA3～5区）白质密度,以及双侧枕叶（BA17～19区）、左侧扣带回后部（BA23,30,31区）和左侧中央旁小叶（BA3～5区）白质体积均增加,且左侧扣带回后部白质密度增加与嗅觉识别阈值呈负相关（rs=0．496,P=0．010）。结论原发性帕金森病患者嗅觉功能明显减退,但与年龄及病程均无相关性。有嗅觉减退的早期帕金森病患者其嗅觉相关脑区,尤其是神经纤维通过的白质脑区存在明显的病理变化,可能提示帕金森病患者嗅觉障碍是中枢神经变性的结果。与此同时,VBM法作为一种客观分析方法,弥补了兴趣区分析法的缺点,可以广泛用于帕金森病或神经变性疾病的诊断分析。     

帕金森病患者嗅觉障碍与嗅觉相关脑区结构变化关系的研究

目的利用基于体素的形态学分析(VBM)研究原发性帕金森病患者嗅觉相关脑区结构改变及其与嗅觉障碍之间的关系,探讨其作为早期诊断的可能性。方法应用"五味嗅觉测试液"对26例诊断明确的早期原发性帕金森病患者进行嗅觉功能检测,并与年龄、病程和病情严重程度[帕金森病统一评价量表(UPDRS)]进行相关分析。磁化准备快速梯度回波序列获取三维结构图像,SPM5软件后处理,通过配准、分割获得白质密度图像,经调试获得白质体积图像。结果帕金森病组患者嗅觉察觉阈值和嗅觉识别阈值分别为0.66±0.84和2.41±0.74,显著高于对照组的-0.64±0.83和1.08±0.54(Z=4.455,P=0.000;t=4.898,P=0.000)。帕金森病组患者嗅觉功能与年龄(察觉阈值:r_s=0.199,P=0.330;识别阈值:r_s=0.256,P=0.207)、病程(察觉阈值:r_s=0.123,P=0.550;识别阈值:r_s=0.055,P=0.789)及UPDRSⅢ评分(察觉阈值:r_s=0.229,P=0.260;识别阈值:r_s=0.379,P=0.056)无明显相关性;UPDRS总评分与嗅觉察觉阈值无相关性(r_s=0.314,P=0.118),但与嗅觉识别阈值呈正相关(r_s=0.397,P=0.045)。与对照组相比,原发性帕金森病组患者右侧枕叶(BA17～19区)、左侧扣带回后部(BA23,30,31区)、左侧枕叶(BA18,19区)和左侧中央旁小叶(BA3～5区)白质密度,以及双侧枕叶(BA17～19区)、左侧扣带回后部(BA23,30,31区)和左侧中央旁小叶(BA3～5区)白质体积均增加,且左侧扣带回后部白质密度增加与嗅觉识别阈值呈负相关(r_s=0.496,P=0.010)。结论原发性帕金森病患者嗅觉功能明显减退,但与年龄及病程均无相关性。有嗅觉减退的早期帕金森病患者其嗅觉相关脑区,尤其是神经纤维通过的白质脑区存在明显的病理变化,可能提示帕金森病患者嗅觉障碍是中枢神经变性的结果。与此同时,VBM法作为一种客观分析方法,弥补了兴趣区分析法的缺点,可以广泛用于帕金森病或神经变性疾病的诊断分析。     

帕金森病嗅觉障碍研究进展

帕金森病（Parkinsondisease，PD）的主要临床特征为运动症状，但近年来其非运动性症状日益收到重视。嗅觉功能障碍是PD主要的非运动症状之一。据统计，90％的PD患者运动症状出现前表现有不同程度嗅觉功能减退或完全性嗅觉丧失。     

吸烟与帕金森病嗅觉障碍

帕金森病是临床常见的神经变性病,根据临床症状可以分为运动症状和非运动症状,嗅觉障碍作为帕金森病最常见的非运动症状越来越受到重视。既往研究显示,尼古丁可能降低帕金森病发病风险,而有吸烟史的帕金森病患者嗅觉障碍轻微,因此吸烟可能通过嗅觉系统对帕金森病产生保护作用。吸烟对帕金森病患者嗅觉功能的影响可能有助于我们更全面地了解帕金森病发病过程。     

吸烟对帕金森病患者嗅觉障碍的影响

目的探讨吸烟对帕金森病(PD)患者嗅觉障碍的影响。方法根据吸烟情况将167例PD患者(PD组)及100例正常人(正常对照组)分为吸烟亚组及不吸烟亚组。采用TT嗅觉测试液对入组者进行嗅素识别阈值测定。结果与正常对照组比较,PD组MMSE评分及蒙特利尔认知评估(Mo CA)评分显著降低(均P0.05),两组年龄、吸烟史及男性比率未见明显差异(均P0.05)。PD组嗅素识别阈显著高于正常对照组(t=6.785,P=0.000)。与PD吸烟亚组比较,不吸烟亚组嗅素识别阈显著升高(t=-3.000,P=0.003)。正常人吸烟亚组较不吸烟亚组嗅素识别阈值减低,但无统计学意义(t=0.784,P=0.435)。PD吸烟者嗅觉阈值与吸烟年限、吸烟总量无相关(r=-0.104,P=0.441;r=-0.156,P=0.246)。结论吸烟可能对PD患者嗅觉有保护作用,并且与吸烟年限、吸烟总量无关。     

嗅觉障碍与常见神经认知障碍的研究进展

嗅觉障碍在老年人中患病率较高,不仅影响人的生活质量及心理健康,而且是多种神经精神疾病的临床表现,尤其是阿尔茨海默病(Alzheimer's disease,AD)等神经认知障碍。AD是一种常见的以进行性痴呆为主要表现的神经退行性疾病,无法治愈,给个人、家庭及社会带来沉重的负担。通过AD标志物检测,早期发现,早期干预,对延缓AD进展大有帮助。嗅觉障碍与AD及轻度认知障碍(mild cognitive impairment,MCI)密切相关,嗅觉功能检测或许能辅助早期识别MCI及AD,因此我们将重点综述嗅觉障碍与MCI及AD常规诊断手段相关联的最新研究进展,以评估嗅觉障碍在MCI及AD等常见神经认知障碍研究中的价值。     

Depth of olfactory sulcus and olfactory function

The aim of this study was to identify whether the depth of the olfactory sulcus relates to olfactory function in healthy subjects. Forty-four healthy, male volunteers (age range 22-45 years, mean age 28.3 years) were included in this study. Olfactory function was measured for phenyl ethyl alcohol odor thresholds, odor discrimination, and odor identification. Magnetic resonance imaging of the olfactory sulcus was performed immediately following olfactometry. Based on previous investigations the depth of the olfactory sulcus was measured in the plane of the posterior tangent through the eyeballs. Olfactory function correlated significantly with left-sided depth of the olfactory sulcus (r(44)=0.33, P=0.03); no such correlation was seen for the right side. In addition, olfactory sulcus depth was found to be significantly deeper on the right compared to the left side (t=5.61, P<0.001). The present results suggest that there is small, but significant relation between morphological brain structures and measures of olfactory function. Further, lateralization of olfactory sulcus depth may correlate to functional lateralization in the olfactory system. Thus, it may be carefully speculated that sensory input in the olfactory system results in cortical growth in the area of the olfactory sulcus, at least at some developmental stage.     

Comparative gene expression profiling of olfactory ensheathing cells from olfactory bulb and olfactory mucosa

Olfactory ensheathing cells (OEC) have the ability to promote regeneration in the nervous system. Hence, they hold promise for cell therapy. Most of the experimental studies have investigated the role of OECs taken from olfactory bulb (OB). However, for a clinical human application, olfactory mucosa (OM) seems to be the only acceptable source for OECs. Many studies have compared the distinct ability of OECs from OB and OM to improve functional nerve regeneration after lesion of the nervous system. Nevertheless, the two populations of OECs may differ in several points, which might affect all fate after transplantation in vivo. We report here the first study which compares gene expression profiling between these two populations of OECs. It appears that OB‐OECs and OM‐OECs display distinct gene expression pattern, which suggest that they may be implicated in different physiological processes. Notably, OM‐OECs overexpress genes characteristic of wound healing and regulation of extra cellular matrix. In contrast, OB‐OECs gene profile suggests a prominent role in nervous system development. Hence, OB‐OECs and OM‐OECs fundamentally differ in their gene expression pattern, which may represent a crucial point for future clinical application. © 2010 Wiley‐Liss, Inc.     

Amphibian olfactory receptor neurons express olfactory marker protein

Expression of olfactory marker protein (OMP) in olfactory receptor neurons (ORNs) in two amphibians was investigated by immunohistochemical methods. The OMP immunoreactivity was observed in the cilia, apical dendritic knobs, dendrites and somas of ORNs; the axons of ORNs also showed intense immunoreactivity for OMP throughout their course from the olfactory epithelium to the glomerular layer of the olfactory bulb. Seven days after olfactory nerve transection in salamander, the number of OMP-positive ORNs was markedly reduced in the ipsilateral epithelium. The results demonstrate that amphibian ORNs express OMP and confirm its phylogenetic conservation across diverse species.     

Changes in olfactory bulb volume following lateralized olfactory training

Repeated exposure to odors modifies olfactory function. Consequently, “olfactory training” plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19–43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the “Sniffin‘ Sticks” test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.     

Ultrastructural changes in olfactory receptor neurons following olfactory nerve section

Unilateral olfactory nerve section was performed in the salamander, Ambystoma tigrinum. An ultrastructural study was performed to investigate the changes occuring during degeneration and replacement of the mature olfactory receptor neurons. Experimental and contralateral control tissues were examined following postoperative survival periods ranging from 12 hours to 90 days. Normal bipolar receptor neurons have a fusiform cell body containing a thin rim of cytoplasm and an ovoid nucleus with a characteristic “checkerboard” chromatin pattern. A single apical dendrite projects to the surface of the epithelium, where numerous cilia extend from its apex into the overlying mucus. A single, unmyelinated, unbranching axon originates at the basal pole of the cell. After nerve section, retrograde degeneration of the mature neurons occurs. Early degenerative changes include pronounced condensation of the nuclear chromatin, increased number of nuclear membrane infoldings, and dilation of the space between the membranes of the nuclear envelope. At a later stage, the cytoplasm of the cell increases in volume and its organelle systems break down, resulting in accumulation of various forms of cell inclusions. Subsequently, proliferation of cells in the basal region of the epithelium occurs. Between 3 week and 2 months following nerve section, these cells differentiate into mature neurons. By 3 months, neurons within the epithelium have resumed their normal ultrastructure. Correlation of the time course of the ultrastructural changes with previously reported neurophysiological studies indicates that neuronal activity of the epithelium is dependent upon the presence of fully differentiated olfactory neurons.     

Naris occlusion alters olfactory marker protein immunoreactivity in olfactory epithelium

Though its function remains obscure, olfactory marker protein (OMP) has been implicated in olfactory transduction and the enhancement of neurogenesis within olfactory epithelium. Here we show, using Western blot analysis and immunocytochemistry, that unilateral naris occlusion (UNO) on postnatal day 1 alters OMP immunoreactivity (IR) differentially on the occluded and non-occluded sides of the nasal cavity in 18, 24 and 70-day-old mice. Compared to untreated animals, UNO-treated animals had a decrease in OMP-IR in olfactory receptor neurons on the non-occluded side and an increase in OMP-IR in olfactory receptor neurons on the occluded side of the nasal cavity. These results suggest that OMP concentration is up- or down-regulated depending on the amount of odor stimulation olfactory receptor neurons receive. It is proposed that this apparent change in protein concentration may be part of a more general compensatory response by olfactory neurons to levels of odor in the environment.     

Reduced olfactory bulb volume in post-traumatic and post-infectious olfactory dysfunction

The olfactory bulb is a highly plastic structure the volume of which partly reflects the degree of afferent neural activity. In this study, 22 patients with post-infectious olfactory deficit, nine participants with post-traumatic olfactory deficit, and 17 healthy controls underwent magnetic resonance volumetry of the olfactory bulb. Patients presented with significantly smaller olfactory bulb volumes than controls; significant correlations between olfactory function and bulb volume were observed. Patients with parosmia exhibited smaller olfactory bulb volumes than those without parosmia. Findings indicate that smell deficits leading to a reduced sensory input to the olfactory bulb result in structural changes at the level of the bulb. Reduced olfactory bulb volumes may also be considered to be characteristic of parosmia.     

Projections of olfactory bulbs to the olfactory and vomeronasal cortices

Projections from the olfactory bulbs have been traditionally described as 'nontopographically organized'. Olfactory and vomeronasal projections have been reported to reach nonoverlapping cortical areas. Four receptor expression zones have been described in the olfactory epithelium, maintained in the main olfactory bulb, but none in the olfactory cortex. Recent data have demonstrated convergence in the basal telencephalon of olfactory and vomeronasal projections. Injections of methanesulfonate hydroxystilbamidine (FluoroGold) in the chemosensory cortex were done to map retrograde labeling in the bulbs. Topography was not observed in the four zones of the main olfactory bulb. Areas of the rostral telencephalon were shown to receive simultaneous inputs from the main and accessory olfactory bulbs.