\u03b1-synuclein inclusions are abundant in non-neuronal cells in the anterior olfactory nucleus of the Parkinson\u2019s disease olfactory bulb

Taylor J Stevenson,Richard L M Faull,Maurice A Curtis,Birger V Dieriks,Helen C Murray,Clinton Turner

doi:10.1038/s41598-020-63412-x

Taylor J Stevenson, Richard L M Faull + Show 4 more

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https://doi.org/10.1038/s41598-020-63412-x

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Journal: Scientific Reports	Publication Date: Apr 21, 2020
Citations: 43	License type: open-access

Affiliation: University of Auckland, Auckland City Hospital

Abstract

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.

Highlights

Parkinson’s disease (PD) is clinically diagnosed by the presence of four cardinal motor symptoms: bradykinesia, tremor, rigidity and postural instability
As the disease progresses into stage II, α-syn pathology is evident in the brainstem where it reaches the substantia nigra in stage III, coinciding with the clinical motor symptoms associated with PD5
To confidently identify the anterior olfactory nucleus (AON) regions across different sections and cases, we found that the co-labelling of Hoechst, NeuN, PGP9.5 and CNPase was sufficient

Summary

Introduction

Parkinson’s disease (PD) is clinically diagnosed by the presence of four cardinal motor symptoms: bradykinesia, tremor, rigidity and postural instability. In stage I, the dorsal motor nucleus of the vagus nerve and the olfactory system – olfactory mucosa, olfactory bulb (OFB) and regions of the anterior olfactory nucleus (AON) present α-syn pathology. Many in vitro and in vivo models have suggested that neuronal cells are the main facilitator for the spread of α-syn pathology following the major neuronal pathways in the brain[17,18,19]. These studies point toward the AON and OFB as being crucial structures for the spread of α-syn pathology. What of other cell types that may spread, but may not aggregate α-syn?

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