| Autor: |
Nash KR; Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, Florida, USA., Moran P; Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, Florida, USA., Finneran DJ; Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, Florida, USA., Hudson C; James A. Haley Veterans Affairs Hospital, Research Service, Department of Neurosurgery and Brain Repair, and Center of Excellence for Aging and Brain Repair USF, Tampa, Florida, USA., Robinson J; Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, Florida, USA., Morgan D; Molecular Pharmacology and Physiology Department, Byrd Alzheimer Institute, University of South Florida, Tampa, Florida, USA., Bickford PC; James A. Haley Veterans Affairs Hospital, Research Service, Department of Neurosurgery and Brain Repair, and Center of Excellence for Aging and Brain Repair USF, Tampa, Florida, USA. |
| Abstrakt: |
In Parkinson's disease, α-synuclein is known to activate microglia and this activation has been proposed as one of the mechanisms of neurodegeneration. There are several signals produced by neurons that have an anti-inflammatory action on microglia, including CX3CL1 (fractalkine). We have shown that a soluble form of CX3CL1 is required to reduce neuron loss in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and that fractalkine agonism can reduce neuron loss in a 6-hydroxydopamine lesion model. Here, we show that fractalkine can reduce α-synuclein-mediated neurodegeneration in rats. Rats that received fractalkine showed abrogated loss of tyrosine hydroxylase and Neu-N staining. This was replicated in animals where we expressed fractalkine from astrocytes with the glial fibrillary acid protein (GFAP) promoter. Interestingly, we did not observe a reduction in MHCII expression suggesting that soluble fractalkine is likely altering the microglial state to a more neuroprotective one rather than reducing antigen presentation. |
