Christopher J Wheeler, Akop Seksenyan, Yosef Koronyo, Altan Rentsendorj, Danielle Sarayba, Henry Wu, Ashley Gragg, Emily Siegel, Deborah Thomas, Andres Espinosa, Kerry Thompson, Keith Black, Maya Koronyo-Hamaoui, Robert Pechnick and Dwain K Irvin
T-lymphocytes have been previously implicated in protecting dopaminergic neurons in the substantianigra from
induced cell death. However, the role of T-cells in neurodegenerative models such as Parkinson’s disease (PD) has
not been fully elucidated. To examine the role of T-lymphocytes on motor behavior in the 6-hydroxydopamine (6-
OHDA) unilateral striatal partial lesion PD rat model, we assessed progression of hemi-parkinsonian lesions in the
substantia nigra, induced by 6-OHDA striatal injections, in athymic rats (RNU-/-, T-lymphocyte-deficient) as
compared to RNU-/+ rats (phenotypically normal). Motor skills were determined by the cylinder and D-amphetamine
sulfate-induced rotational behavioral tests. Cylinder behavioral test showed no significant difference between
unilaterally lesioned RNU-/- and RNU-/+ rats. However both unilaterally lesioned RNU-/- and RNU-/+ rats favored
the use of the limb ipsilateral to lesion. Additionally, amphetamine-induced rotational test revealed greater rotational
asymmetry in RNU-/- rats compared to RNU-/+ rats at two- and six-week post-lesion. Quantitative
immunohistochemistry confirmed loss of striatal TH-immunopositive fibers in RNU-/- and RNU-/+ rat , as well as
blood-brain-barrier changes associated with PD that may influence passage of immune cells into the central nervous
system in RNU-/- brains. Specifically, GFAP immunopositive cells were decreased, as were astrocytic end-feet
(AQP4) contacting blood vessels (laminin) in the lesioned relative to contralateral striatum. Flow cytometric analysis
in 6-OHDA lesioned RNU-/+rats revealed increased CD4+ and decreased CD8+ T cells specifically within lesioned
brain. These results suggest that both major T cell subpopulations are significantly and reciprocally altered following
6-OHDA-lesioning, and that global T cell deficiency exacerbates motor behavioral defects in this rat model of PD.
