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Cytoarchitectural changes in the olfactory bulb of Parkinson's disease patients.

ABSTRACT: Olfactory dysfunction is associated with nearly all the cases of Parkinson's disease (PD) and typically manifests years before motor symptoms are detected. The cellular mechanisms underlying this dysfunction, however, are not understood. In this study, olfactory bulbs (OBs) from male control and PD subjects were examined by histology for changes in cytoarchitecture. These studies found that the general OB laminar organization and the number of interneurons expressing tyrosine hydroxylase were unaltered. In contrast, the number of mitral/tufted projection neurons and interneurons expressing Calretinin were significantly decreased in PD subjects. This study reveals changes in OB cytoarchitecture mediated by PD and provides valuable insight into identifying specific OB neuronal populations vulnerable to PD-related neurodegeneration.

SUBMITTER: Cave JW

PROVIDER: S-EPMC5516575 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Cytoarchitectural changes in the olfactory bulb of Parkinson's disease patients.

Cave John W JW Fujiwara Nana N Weibman Ava R AR Baker Harriet H

NPJ Parkinson's disease 20160609

Olfactory dysfunction is associated with nearly all the cases of Parkinson's disease (PD) and typically manifests years before motor symptoms are detected. The cellular mechanisms underlying this dysfunction, however, are not understood. In this study, olfactory bulbs (OBs) from male control and PD subjects were examined by histology for changes in cytoarchitecture. These studies found that the general OB laminar organization and the number of interneurons expressing tyrosine hydroxylase were un ...[more]

PMID: 28725697

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Changes in Olfactory Bulb Volume in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Project description:ObjectiveThe changes in olfactory bulb (OB) volume in Parkinson's disease (PD) patients have not yet been comprehensively evaluated. The purpose of this meta-analysis was to explore whether the OB volume was significantly different between PD patients and healthy controls.MethodsPubMed and Embase were searched up to March 6, 2015 with no language restrictions. Two independent reviewers screened eligible studies and extracted data on study characteristics and OB volume. Additionally, a systematic review and meta-analysis using a random-effects model were conducted. Publication bias was determined by using funnel plots and Begg's and Egger's tests. Subgroup analyses were performed to assess possible sources of heterogeneity.ResultsSix original case-control studies of 216 PD patients and 175 healthy controls were analyzed. The pooled weighted mean difference (WMD) in the OB volume between the PD patients and the healthy participants was -8.071 for the right OB and -10.124 for the left OB; these values indicated a significant difference among PD patients compared with healthy controls. In addition, a significant difference in the lateralized OB volume was observed in PD patients, with a pooled WMD of 1.618; these results indicated a larger right OB volume than left OB volume in PD patients. In contrast, no difference in the lateralized OB volume was found in healthy controls. No statistical evidence of publication bias among studies was found based on Egger's or Begg's tests. Sensitivity analyses revealed that the results were consistent and robust.ConclusionsOverall, both the left and the right OB volume were significantly smaller in PD patients than in healthy controls. However, significant heterogeneity and an insufficient number of studies underscore the need for further observational research.

| S-EPMC4762676 | biostudies-literature

Olfactory bulb surroundings can help to distinguish Parkinson's disease from non-parkinsonian olfactory dysfunction.

Project description:BACKGROUND:The olfactory bulb is one of the first regions of insult in Parkinson's disease (PD), consistent with the early onset of olfactory dysfunction. Investigations of the olfactory bulb may, therefore, help early pre-motor diagnosis. We aimed to investigate olfactory bulb and its surrounding regions in PD-related olfactory dysfunction when specifically compared to other forms of non-parkinsonian olfactory dysfunction (NPOD) and healthy controls. METHODS:We carried out MRI-based olfactory bulb volume measurements from T2-weighted imaging in scans from 15 patients diagnosed with PD, 15 patients with either post-viral or sinonasal NPOD and 15 control participants. Further, we applied a deep learning model (convolutional neural network; CNN) to scans of the olfactory bulb and its surrounding area to classify PD-related scans from NPOD-related scans. RESULTS:Compared to controls, both PD and NPOD patients had smaller olfactory bulbs, when measured manually (both p < .001) whereas no difference was found between PD and NPOD patients. In contrast, when a CNN was used to differentiate between PD patients and NPOD patients, an accuracy of 88.3% was achieved. The cortical area above the olfactory bulb which stretches around and into the olfactory sulcus appears to be a region of interest in the differentiation between PD and NPOD patients. CONCLUSION:Measures from and around the olfactory bulb in combination with the use of a deep learning model may help differentiate PD patients from patients with NPOD, which may be used to develop early diagnostic tools based on olfactory dysfunction.

| S-EPMC7567959 | biostudies-literature

A non-invasive olfactory bulb measure dissociates Parkinson's patients from healthy controls and discloses disease duration.

Project description:Olfactory dysfunction is a prevalent non-motor symptom of Parkinson's disease (PD). This dysfunction is a result of neurodegeneration within the olfactory bulb (OB), the first processing area of the central olfactory system, and commonly precedes the characteristic motor symptoms in PD by several years. Functional measurements of the OB could therefore potentially be used as an early biomarker for PD. Here, we used a non-invasive method, so-called electrobulbogram (EBG), to measure OB function in PD and age-matched healthy controls to assess whether EBG measures can dissociate PDs from controls. We estimated the spectrogram of the EBG signal during exposure to odor in PD (n = 20) and age-matched controls (n = 18) as well as identified differentiating patterns of odor-related synchronization in the gamma, beta, and theta frequency bands. Moreover, we assessed if these PD-EBG components could dissociate PD from control as well as their relationship with PD characteristics. We identified six EBG components during the initial and later stages of odor processing which dissociated PD from controls with 90% sensitivity and 100% specificity with links to PD characteristics. These PD-EBG components were related to medication, disease duration, and severity, as well as clinical odor identification performance. These findings support using EBG as a tool to experimentally assess PD interventions, potentially aid diagnosis, and the potential development of EBG into an early biomarker for PD.

| S-EPMC8373926 | biostudies-literature

Metal concentrations and distributions in the human olfactory bulb in Parkinson's disease.

Project description:In Parkinson's disease (PD), the olfactory bulb is typically the first region in the body to accumulate alpha-synuclein aggregates. This pathology is linked to decreased olfactory ability, which becomes apparent before any motor symptoms occur, and may be due to a local metal imbalance. Metal concentrations were investigated in post-mortem olfactory bulbs and tracts from 17 human subjects. Iron (p?<?0.05) and sodium (p?<?0.01) concentrations were elevated in the PD olfactory bulb. Combining laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry, iron and copper were evident at very low levels in regions of alpha-synuclein aggregation. Zinc was high in these regions, and free zinc was detected in Lewy bodies, mitochondria, and lipofuscin of cells in the anterior olfactory nucleus. Increased iron and sodium in the human PD olfactory bulb may relate to the loss of olfactory function. In contrast, colocalization of free zinc and alpha-synuclein in the anterior olfactory nucleus implicate zinc in PD pathogenesis.

| S-EPMC5585381 | biostudies-literature

Astrogliosis and sexually dimorphic neurodegeneration and microgliosis in the olfactory bulb in Parkinson's disease.

Project description:Hyposmia is prodromal, and male sex is a risk marker for an enhanced likelihood ratio of Parkinson's disease. The literature regarding olfactory bulb volume reduction is controversial, although the olfactory bulb has been largely reported as an early and preferential site for α-synucleinopathy. These pathological deposits have been correlated with neural loss in Nissl-stained material. However, microgliosis has rarely been studied, and astrogliosis has been virtually neglected. In the present report, α-synucleinopathy (α-synuclein), neurodegeneration (Neu-N), astrogliosis (GFAP), and microgliosis (Iba-1) were quantified, using specific markers and stereological methods. Disease, sex, age, disease duration, and post-mortem interval were considered variables for statistical analysis. No volumetric changes have been identified regarding disease or sex. α-Synucleinopathy was present throughout the OB, mainly concentrated on anterior olfactory nucleus. Neurodegeneration (reduction in Neu-N-positive cells) was statistically significant in the diseased group. Astrogliosis (increased GFAP labeling) and microgliosis (increased Iba-1 labeling) were significantly enhanced in the Parkinson's disease group. When analyzed per sex, neurodegeneration and microgliosis differences are only present in men. These data constitute the demonstration of sex differences in neurodegeneration using specific neural markers, enhanced astrogliosis and increased microgliosis, also linked to male sex, in the human olfactory bulb in Parkinson's disease.

| S-EPMC7820595 | biostudies-literature

Widespread transneuronal propagation of α-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson's disease.

Project description:Parkinson's disease (PD) is characterized by the progressive appearance of intraneuronal Lewy aggregates, which are primarily composed of misfolded α-synuclein (α-syn). The aggregates are believed to propagate via neural pathways following a stereotypical pattern, starting in the olfactory bulb (OB) and gut. We hypothesized that injection of fibrillar α-syn into the OB of wild-type mice would recreate the sequential progression of Lewy-like pathology, while triggering olfactory deficits. We demonstrate that injected α-syn fibrils recruit endogenous α-syn into pathological aggregates that spread transneuronally over several months, initially in the olfactory network and later in distant brain regions. The seeded inclusions contain posttranslationally modified α-syn that is Thioflavin S positive, indicative of amyloid fibrils. The spreading α-syn pathology induces progressive and specific olfactory deficits. Thus, we demonstrate that propagating α-syn pathology triggered in the OB is functionally detrimental. Collectively, we have created a mouse model of prodromal PD.

| S-EPMC4995088 | biostudies-literature

?-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson's disease olfactory bulb.

Project description:Reduced olfactory function (hyposmia) is one of the most common non-motor symptoms experienced by those living with Parkinson's disease (PD), however, the underlying pathology of the dysfunction is unclear. Recent evidence indicates that ?-synuclein (?-syn) pathology accumulates in the anterior olfactory nucleus of the olfactory bulb years before the motor symptoms are present. It is well established that neuronal cells in the olfactory bulb are affected by ?-syn, but the involvement of other non-neuronal cell types is unknown. The occurrence of intracellular ?-syn inclusions were quantified in four non-neuronal cell types - microglia, pericytes, astrocytes and oligodendrocytes as well as neurons in the anterior olfactory nucleus of post-mortem human PD olfactory bulbs (n?=?11) and normal olfactory bulbs (n?=?11). In the anterior olfactory nucleus, ?-syn inclusions were confirmed to be intracellular in three of the four non-neuronal cell types, where 7.78% of microglia, 3.14% of pericytes and 1.97% of astrocytes were affected. Neurons containing ?-syn inclusions comprised 8.60% of the total neuron population. Oligodendrocytes did not contain ?-syn. The data provides evidence that non-neuronal cells in the PD olfactory bulb contain ?-syn inclusions, suggesting that they may play an important role in the progression of PD.

| S-EPMC7174302 | biostudies-literature

Olfactory bulb proteomics in human Alzheimer's disease

Project description:Olfactory dysfunction is among the earliest features of Alzheimer´s disease (AD). Although neuropathological abnormalities have been detected in the olfactory bulb (OB), little is known about its dynamic biology. Here, OB- proteome analysis was performed across different AD stages using a label-free approach.

2018-01-16 | PXD005319 | Pride

Olfactory bulb volume changes associated with trans-sphenoidal pituitary surgery.

Project description:ObjectiveThe trans-sphenoidal approach is most frequently used for pituitary adenoma (PA) enucleation. However, effects of this surgery on neighboring structures have received little attention so far. In particular, no investigations on olfactory bulb (OB) anatomy after trans-sphenoidal surgery have been reported. Because impairment of olfaction has been shown in small groups following trans-sphenoidal surgery we hypothesized that the transnasal approach is likely to alter OB volume which is associated with changes of olfactory function.MethodsThe study comprised 33 patients with pituitary adenoma (14 women and 19 men, mean age 50 years). Comprehensive assessment of olfactory function was conducted with the "Sniffin' Sticks" test kit. Based on magnetic resonance imaging scans OBs were measured before and approximately one year after trans-sphenoidal PA enucleation.ResultsOwing to postoperative non-compliance and MRI artifacts partly due to drill friction complete evaluation of "Sniffin' Sticks" in term of obtaining the TDI score was possible pre- and postoperatively in 21 patients whereas OB volumes were available in 32 patients. Approximately one year after surgery olfactory function was not significantly different from baseline. However, left- and right-sided OB volume in patients treated via trans-sphenoidal surgery decreased (p = 0.001). The side of the surgical approach did not affect OB volume in a side-specific manner. Changes in odor threshold were significantly correlated to changes in right-sided OB volume (r = 0.45, p = 0.024).ConclusionOverall olfactory performance one year after surgery was not significantly different from baseline. However, changes in OB volume are associated with changes in olfactory performance and OB volumes decreased in patients.

| S-EPMC6919594 | biostudies-literature

Olfactory Dysfunction in Parkinson's Disease Patients with the LRRK2 G2385R Variant.

Project description:Olfactory dysfunction has been reported in Parkinson's disease (PD) patients carrying the LRRK2 G2019S variant in Caucasians but rarely in those with the LRRK2 G2385R variant. In this study, we performed genotyping for the LRRK2 G2385R variant in PD patients recruited from the Movement Disorder Clinic of Xuanwu Hospital in Beijing and in healthy controls randomly selected from the Beijing Longitudinal Study on Aging cohort. The "five-odor olfactory detection array", an olfactory threshold test, was used to assess olfactory function. One hundred and eighty-six participants were enrolled, comprising 43 PD patients without (iPD) and 25 with (LRRK2-PD) the LRRK2 G2385R variant, and 118 healthy controls. Our results showed that the threshold of olfactory identification was significantly worse in PD patients than in controls, but not significantly different between the iPD and LRRK2-PD groups. These findings suggested that although olfactory function in LRRK2-PD patients is impaired, it is similar to that in iPD patients.

| S-EPMC5567486 | biostudies-literature

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