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

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 ?-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.

SUBMITTER: Stevenson TJ

PROVIDER: S-EPMC7174302 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Stevenson Taylor J TJ Murray Helen C HC Turner Clinton C Faull Richard L M RLM Dieriks Birger V BV Curtis Maurice A MA

Scientific reports 20200421 1

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 no ...[more]

PMID: 32317654

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Project description:Parkinson's disease is characterized by a proteinopathy that includes aggregates of α-synuclein. A recent hypothesis proposes a prion-like spreading mechanism for this α-synucleinopathy. Early neuropathological deposits occur, among others, in the anterior olfactory nucleus (AON). This study investigates the anterograde and/or retrograde transmissibility of exogenous α-synuclein inoculated in the right AON of the A53T model of Parkinson's disease and wild-type mice as well as neuronal and glial involvement. Seven experimental groups were established: wild-type injected with tracers; A53T mice injected with either α-synuclein or saline 2 months beforehand; wild-type injected with either α-synuclein or saline 2 months beforehand; and wild-type injected with either α-synuclein or saline 4 months beforehand. Weight and behavioral changes were analyzed. Immunohistochemistry against α-synuclein, NeuN, Iba-1 and GFAP was performed. Volume and marker distributions in the olfactory bulb (OB), AON and piriform cortex were analyzed using unbiased stereology. The behavioral analyses reveal higher levels of hyperactivity in transgenic as compared to wild-type mice. Tract-tracing experiments show that the main contralateral afferent projections to the dorsal AON come from the AON and secondarily from the OB. In saline-injected transgenic animals, α-synuclein expression in the OB and the AON is higher in the left hemisphere than in the right hemisphere, which could be due to basal interhemispheric differences. α-synuclein injection could provoke a significant increase in the left hemisphere of the transgenic mice's OB, compared to saline-injected animals. Neuronal loss was observed in saline-injected transgenic mice relative to the saline-injected wild-type group. There were no overall differences in neuron number following injection of α-synuclein into either wild-type or transgenic mice, however some neuron loss was apparent in specific regions of α-synuclein injected wild-types. Microglia labeling appeared to be correlated with surgery-induced inflammation. Astroglial labeling was higher in transgenic animals, which could be due to endogenous α-synucleinopathy. This study suggests α-synucleinopathy induction, via retrograde and contralateral projections, within the olfactory system of transgenic animals.

Dataset Information

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

Publications

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

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