title: T-Lymphocyte Deficiency Exacerbates Behavioral Deficits in the 6-OHDA Unilateral Lesion Rat Model for Parkinson's Disease.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wheeler
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Akop
authors.initials: A
authors.lastname: Seksenyan
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Koronyo
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Altan
authors.initials: A
authors.lastname: Rentsendorj
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Sarayba
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Gragg
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Siegel
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Espinosa
authors.affiliation: Department of Biology, Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Thompson
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Black
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Koronyo-Hamaoui
authors.affiliation: Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific Western University of Health Sciences, Pomona, CA 91766, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pechnick
authors.affiliation: Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA, Department of Psychiatry, Cedars-Sinai Medical Center, Los Angeles, California, 90048, USA; Occidental College, Los Angeles, CA 90041, USA.
authors.forename: Dwain K
authors.initials: DK
authors.lastname: Irvin