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

Gardner, Bronwen; Dieriks, Birger; Cameron, S. D.; Mendis, Lakshini; Turner, Clinton; Faull, Richard L. M.; Curtis, Maurice A.

doi:10.1038/s41598-017-10659-6

Cited by 33 publications

(27 citation statements)

References 103 publications

(103 reference statements)

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“…One of the most common non-motor symptoms that is present in more than 90% of those suffering with PD is the loss of olfaction (hyposmia or anosmia depending on severity) 6 . Prior to the changes seen in the substantia nigra, α-syn pathology is present throughout the OFB and tract and is especially abundant in each compartment of the AON 5,7,8 . The AON is the neural conduit between the OFB and the piriform cortex, entorhinal cortex, amygdala and hippocampal formations 9,10 .…”

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confidence: 99%

α-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson’s disease olfactory bulb

Stevenson

Murray

Turner

et al. 2020

Sci Rep

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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 α-synuclein (α-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 α-syn, but the involvement of other non-neuronal cell types is unknown. the occurrence of intracellular α-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, α-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 α-syn inclusions comprised 8.60% of the total neuron population. oligodendrocytes did not contain α-syn. the data provides evidence that non-neuronal cells in the pD olfactory bulb contain α-syn inclusions, suggesting that they may play an important role in the progression of pD.

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confidence: 99%

α-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson’s disease olfactory bulb

Stevenson

Murray

Turner

et al. 2020

Sci Rep

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“…It (Wood, Bilclough, Bowron, & Walker, ) has been reported that depression was occurred in 10%–45% PD patients, this is consistent with the results that 20 (30.3%) patients with depression and anxiety in this study. Olfactory function became apparent before any motors symptoms, which may be caused by local metal imbalance (Gardner et al., ). But may be due to the less number of cases in this study, the percentage of olfactory dysfunction in the study was 5 (7.6%).…”

Section: Discussionmentioning

confidence: 99%

“…In the past, motor symptoms of Parkinson were focused on, while it has been rarely mentioned, but these non-motor symptoms can seriously affect the life quality of patients with PD (Gardner et al, 2017;Mu et al, 2017;Muzerengi, Contrafatto, & Chaudhuri, 2007). All PD patients basically had different degrees of sleep disorders, most of them occurred at the early stages (Chaudhuri, 2003).…”

Section: Discussionmentioning

confidence: 99%

Ceruloplasmin in Parkinson's disease and the nonmotor symptoms

et al. 2018

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ObjectivesTo investigate the relationship between ceruloplasmin (CP) and Parkinson's disease (PD), and the correlation between CP level and the time difference between nonmotor symptoms and motor symptoms and the diagnosis were also mentioned.Materials and MethodsSixty‐six patients diagnosed with PD for the first time were included in the study. They were divided into CP reduction group (31 cases) and CP normal group (35 cases) according to their CP level. The estimated time difference between nonmotor symptoms and motor symptoms and the diagnosis were recorded respectively. The magnetic sensitive nigra phase value was measured by susceptibility weighted imaging (SWI).ResultsCeruloplasmin level was middling correlated with age (r = .561, p < .001). There was strong negative correlation between CP level and UPDRS scores (r = −.727, p < .001). The CP level was significantly correlated with the magnetic sensitive nigra phase value (r = .891, p < .001). CP level showed moderate correlation with the time difference from nonmotor symptoms to motor symptoms (r = .559, p < .001), besides, the time difference between nonmotor symptoms and the diagnosis (r = .525, p < .001) and CP level was also moderately related.ConclusionsCeruloplasmin interference in iron metabolism was closely related with PD development. And there were slight corrections between CP level and the time difference from nonmotor symptoms to motor symptoms or the diagnosis.

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“…Free Ca 2+ concentrations in rat olfactory neurons reach ≈2 μ M during nerve stimulation [ 30 ]. Likewise, pools of Cu 2+ are released in and around olfactory neurons during signaling, reaching concentrations as high as 10 μ M in the synapse [ 31 – 34 ]. Further, despite high Cu 2+ concentrations, the olfactory bulb in rats does not have elevated expression of the typical copper chaperone metallothionein [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Human S100A5 binds Ca2+ and Cu2+ independently

Wheeler

Harms

2017

BMC Biophys

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BackgroundS100A5 is a calcium binding protein found in a small subset of amniote tissues. Little is known about the biological roles of S100A5, but it may be involved in inflammation and olfactory signaling. Previous work indicated that S100A5 displays antagonism between binding of Ca2+ and Cu2+ ions—one of the most commonly cited features of the protein. We set out to characterize the interplay between Ca2+ and Cu2+ binding by S100A5 using isothermal titration calorimetry (ITC), circular dichroism spectroscopy (CD), and analytical ultracentrifugation (AUC).ResultsWe found that human S100A5 is capable of binding both Cu2+ and Ca2+ ions simultaneously. The wildtype protein was extremely aggregation-prone in the presence of Cu2+ and Ca2+. A Cys-free version of S100A5, however, was not prone to precipitation or oligomerization. Mutation of the cysteines does not disrupt the binding of either Ca2+ or Cu2+ to S100A5. In the Cys-free background, we measured Ca2+ and Cu2+ binding in the presence and absence of the other metal using ITC. Saturating concentrations of Ca2+ or Cu2+ do not disrupt the binding of one another. Ca2+ and Cu2+ binding induce structural changes in S100A5, which are measurable using CD spectroscopy. We show via sedimentation velocity AUC that the wildtype protein is prone to the formation of soluble oligomers, which are not present in Cys-free samples.ConclusionsS100A5 can bind Ca2+ and Cu2+ ions simultaneously and independently. This observation is in direct contrast to previously-reported antagonism between binding of Cu2+ and Ca2+ ions. The previous result is likely due to metal-dependent aggregation. Little is known about the biology of S100A5, so an accurate understanding of the biochemistry is necessary to make informed biological hypotheses. Our observations suggest the possibility of independent biological functions for Cu2+ and Ca2+ binding by S100A5.Electronic supplementary materialThe online version of this article (doi:10.1186/s13628-017-0040-y) contains supplementary material, which is available to authorized users.

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

Cited by 33 publications

References 103 publications

α-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson’s disease olfactory bulb

α-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson’s disease olfactory bulb

Ceruloplasmin in Parkinson's disease and the nonmotor symptoms

Human S100A5 binds Ca2+ and Cu2+ independently

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