T-Lymphocyte Deficiency Exacerbates Behavioral Deficits in the 6-OHDA Unilateral Lesion Rat Model for Parkinson’s Disease
| Autor: | Andres Espinosa, Dwain K. Irvin, Kerry Thompson, Keith L. Black, Yosef Koronyo, Deborah Thomas, Maya Koronyo-Hamaoui, Christopher J. Wheeler, Henry Wu, Emily Siegel, Altan Rentsendorj, Danielle Sarayba, Akop Seksenyan, Ashley Gragg, Robert N. Pechnick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Parkinson's disease business.industry T cell Central nervous system Dopaminergic Substantia nigra Striatum medicine.disease T cell deficiency Article Lesion 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure nervous system medicine medicine.symptom business 030217 neurology & neurosurgery 030304 developmental biology |
| Zdroj: | Journal of neurology & neurophysiology |
| ISSN: | 2155-9562 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|