| First Author | Flores-Cuadrado A | Year | 2019 |
| Journal | Acta Neuropathol Commun | Volume | 7 |
| Issue | 1 | Pages | 56 |
| PubMed ID | 30987677 | Mgi Jnum | J:290927 |
| Mgi Id | MGI:6443514 | Doi | 10.1186/s40478-019-0713-7 |
| Citation | Flores-Cuadrado A, et al. (2019) Neurodegeneration and contralateral alpha-synuclein induction after intracerebral alpha-synuclein injections in the anterior olfactory nucleus of a Parkinson's disease A53T mouse model. Acta Neuropathol Commun 7(1):56 |
| abstractText | Parkinson's disease is characterized by a proteinopathy that includes aggregates of alpha-synuclein. A recent hypothesis proposes a prion-like spreading mechanism for this alpha-synucleinopathy. Early neuropathological deposits occur, among others, in the anterior olfactory nucleus (AON). This study investigates the anterograde and/or retrograde transmissibility of exogenous alpha-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 alpha-synuclein or saline 2 months beforehand; wild-type injected with either alpha-synuclein or saline 2 months beforehand; and wild-type injected with either alpha-synuclein or saline 4 months beforehand. Weight and behavioral changes were analyzed. Immunohistochemistry against alpha-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, alpha-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. alpha-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 alpha-synuclein into either wild-type or transgenic mice, however some neuron loss was apparent in specific regions of alpha-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 alpha-synucleinopathy. This study suggests alpha-synucleinopathy induction, via retrograde and contralateral projections, within the olfactory system of transgenic animals. |
