Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV
The dopaminergic system is especially vulnerable to the effects of human immunodeficiency virus (HIV) infection, rendering dopaminergic deficits early surrogate markers of HIV-associated neuropathology. We quantified dopamine D 2/3 receptors in young HIV-1 transgenic (Tg) ( n = 6) and age-matched co...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publications
2014-11-01
|
| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2014.00031 |
| _version_ | 1797283810619949056 |
|---|---|
| author | Dianne E. Lee William C. Reid Wael G. Ibrahim Kristin L. Peterson Margaret R. Lentz Dragan Maric Peter L. Choyke Elaine M. Jagoda Dima A. Hammoud |
| author_facet | Dianne E. Lee William C. Reid Wael G. Ibrahim Kristin L. Peterson Margaret R. Lentz Dragan Maric Peter L. Choyke Elaine M. Jagoda Dima A. Hammoud |
| author_sort | Dianne E. Lee |
| collection | DOAJ |
| description | The dopaminergic system is especially vulnerable to the effects of human immunodeficiency virus (HIV) infection, rendering dopaminergic deficits early surrogate markers of HIV-associated neuropathology. We quantified dopamine D 2/3 receptors in young HIV-1 transgenic (Tg) ( n = 6) and age-matched control rats ( n = 7) and adult Tg ( n = 5) and age-matched control rats ( n = 5) using [ 18 F]fallypride positron emission tomography (PET). Regional uptake was quantified as binding potential ( BP ND ) using the two-tissue reference model with the cerebellum as the reference. Time-activity curves were generated for the ventral striatum, dorsal striatum, thalamus, and cerebellum. Whereas BP ND values were significantly lower in the ventral striatum ( p < .001) and dorsal striatum ( p = .001) in the adult Tg rats compared to controls rats, they were significantly lower only in the dorsal striatum ( p < .05) in the young rats. Tg rats had smaller striatal volumes on magnetic resonance imaging. We also found lower expression levels of tyrosine hydroxylase on immunohistochemistry in the Tg animals. Our findings suggest that progressive striatal D 2/3 receptor deficits occur in Tg rats as they age and can be detected using small-animal PET imaging. The effectiveness of various approaches in preventing or halting this dopaminergic loss in the Tg rat can thus be measured preclinically using [ 18 F]fallypride PET as a molecular imaging biomarker of HIV-associated neuropathology. |
| first_indexed | 2024-03-07T17:37:13Z |
| format | Article |
| id | doaj.art-9cf9a32a11c549708dc554faef5e8f55 |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2024-03-07T17:37:13Z |
| publishDate | 2014-11-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-9cf9a32a11c549708dc554faef5e8f552024-03-02T16:42:57ZengSAGE PublicationsMolecular Imaging1536-01212014-11-011310.2310/7290.2014.0003110.2310_7290.2014.00031Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIVDianne E. LeeWilliam C. ReidWael G. IbrahimKristin L. PetersonMargaret R. LentzDragan MaricPeter L. ChoykeElaine M. JagodaDima A. HammoudThe dopaminergic system is especially vulnerable to the effects of human immunodeficiency virus (HIV) infection, rendering dopaminergic deficits early surrogate markers of HIV-associated neuropathology. We quantified dopamine D 2/3 receptors in young HIV-1 transgenic (Tg) ( n = 6) and age-matched control rats ( n = 7) and adult Tg ( n = 5) and age-matched control rats ( n = 5) using [ 18 F]fallypride positron emission tomography (PET). Regional uptake was quantified as binding potential ( BP ND ) using the two-tissue reference model with the cerebellum as the reference. Time-activity curves were generated for the ventral striatum, dorsal striatum, thalamus, and cerebellum. Whereas BP ND values were significantly lower in the ventral striatum ( p < .001) and dorsal striatum ( p = .001) in the adult Tg rats compared to controls rats, they were significantly lower only in the dorsal striatum ( p < .05) in the young rats. Tg rats had smaller striatal volumes on magnetic resonance imaging. We also found lower expression levels of tyrosine hydroxylase on immunohistochemistry in the Tg animals. Our findings suggest that progressive striatal D 2/3 receptor deficits occur in Tg rats as they age and can be detected using small-animal PET imaging. The effectiveness of various approaches in preventing or halting this dopaminergic loss in the Tg rat can thus be measured preclinically using [ 18 F]fallypride PET as a molecular imaging biomarker of HIV-associated neuropathology.https://doi.org/10.2310/7290.2014.00031 |
| spellingShingle | Dianne E. Lee William C. Reid Wael G. Ibrahim Kristin L. Peterson Margaret R. Lentz Dragan Maric Peter L. Choyke Elaine M. Jagoda Dima A. Hammoud Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV Molecular Imaging |
| title | Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV |
| title_full | Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV |
| title_fullStr | Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV |
| title_full_unstemmed | Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV |
| title_short | Imaging Dopaminergic Dysfunction as a Surrogate Marker of Neuropathology in a Small-Animal Model of HIV |
| title_sort | imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small animal model of hiv |
| url | https://doi.org/10.2310/7290.2014.00031 |
| work_keys_str_mv | AT dianneelee imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT williamcreid imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT waelgibrahim imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT kristinlpeterson imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT margaretrlentz imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT draganmaric imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT peterlchoyke imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT elainemjagoda imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv AT dimaahammoud imagingdopaminergicdysfunctionasasurrogatemarkerofneuropathologyinasmallanimalmodelofhiv |