NDLI: Complex Changes in the Innate and Adaptive Immunity Accompany Progressive Degeneration of the Nigrostriatal Pathway Induced by Intrastriatal Injection of 6-Hydroxydopamine in the Rat

Content Provider	Springer Nature Link
Author	Ambrosi, Giulia Kustrimovic, Natasa Siani, Francesca Rasini, Emanuela Cerri, Silvia Ghezzi, Cristina Dicorato, Giuseppe Caputo, Sofia Marino, Franca Cosentino, Marco Blandini, Fabio
Copyright Year	2017
Abstract	We investigated changes in innate and adaptive immunity paralleling the progressive nigrostriatal damage occurring in a neurotoxic model of Parkinson’s disease (PD) based on unilateral infusion of 6-hydroxydopamine (6-OHDA) into the rat striatum. A time-course analysis was conducted to assess changes in morphology (activation) and cell density of microglia and astrocytes, microglia polarization (M1 vs. M2 phenotype), lymphocyte infiltration in the lesioned substantia nigra pars compacta (SNc), and modifications of CD8+ and subsets of CD4+ T cell in peripheral blood accompanying nigrostriatal degeneration. Confirming previous results, we observed slightly different profiles of activation for astrocytes and microglia paralleling nigral neuronal loss. For astrocytes, morphological changes and cell density increases were mostly evident at the latest time points (14 and 28 days post-surgery), while moderate microglia activation was present since the earliest time point. For the first time, in this model, we described the time-dependent profile of microglia polarization. Activated microglia clearly expressed the M2 phenotype in the earlier phase of the experiment, before cell death became manifest, gradually shifting to the M1 phenotype as SNc cell death started. In parallel, a reduction in the percentage of circulating CD4+ T regulatory (Treg) cells, starting as early as day 3 post-6-OHDA injection, was detected in 6-OHDA-injected rats. Our data show that nigrostriatal degeneration is associated with complex changes in central and peripheral immunity. Microglia activation and polarization, Treg cells, and the factors involved in their cross-talk should be further investigated as targets for the development of therapeutic strategies for disease modification in PD.
Starting Page	71
Ending Page	81
Page Count	11
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	32
Issue Number	1
e-ISSN	14763524
Language	English
Publisher	Springer US
Publisher Date	2017-03-11
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson’s disease 6-OHDA Rat Microglia Astrocytes T regulatory cells Neurosciences Neurology Neurochemistry Pharmacology/Toxicology Neurobiology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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