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.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is most common in patients over 65 years old, occurs in approximately 2 out of 1,000 people in the western hemisphere
We demonstrate by flow cytometry that CD4+/CD8+ T cell ratio in brains of 6-OHDA-lesioned immunocompetent rats compared to unlesioned controls is increased, which differs from findings in previous studies, but is consistent with a role for T cells in disease progression
Our goal was to examine whether T cell deficiency affects PD progression, and changes the blood-brain barrier (BBB) structure that could conceivably affect their extravasation
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is most common in patients over 65 years old, occurs in approximately 2 out of 1,000 people in the western hemisphere. PD is characterized by the progressive loss of midbrain dopamine neurons in the substantianigra, which causes motor dysfunction amongst other disorders. There has been growing evidence that adaptive immunity may play a role in PD progression as well as other neurodegenerative disorders including Alzheimer’s disease. The adaptive immune response may provide antigen-specific neuroprotection critical for brain repair. T cells act as the mediators of adaptive cellular immunity, allowing the body to mount increasingly potent responses to antigens of infected, transformed, or damaged self-cells with each encounter. A current debate in PD centers upon whether and how the adaptive immune response is involved in PD etiology and/or progression. The exact role of T cells in aggregate (i.e., as they normally co-exist) has not been elucidated [1,2]
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