Mapping reactive astrogliosis in Parkinson's brain with astroglial tracers BU99008 and Deprenyl: New insights from a multi-marker postmortem study

Abstract

BACKGROUND

Despite significant astrocytic involvement in Parkinson's disease (PD), the knowledge regarding the role of reactive astrogliosis is still at the surface level; largely due to lack of specific biomarkers to track these processes. Novel astroglial PET-tracers BU99008 and Deprenyl, hold immense potential for visualizing reactive astrogliosis in PD. However, they have not been thoroughly investigated in PD.

METHODS

We employed a multi-marker approach and performed in vitro radioligand binding and autoradiography studies with ³H-BU99008 and ³H-Deprenyl together with astrocytic immunofluorescence and morphometric analyses in the frontal cortex, temporal cortex, caudate and putamen brain regions of PD (n = 4) and control (n = 7) cases.

RESULTS AND DISCUSSION

³H-BU99008 and ³H-Deprenyl showed distinct binding behavior and displayed a diverse array of binding sites (single or multiple) in PD and control brains. Importantly, ³H-BU99008 and ³H-Deprenyl autoradiography studies captured pronounced reactive astrogliosis in PD brain regions, corroborated by marked changes in astrocytic markers, morphology, and cellular processes.

Highlights

• Astroglial tracers BU99008 and Deprenyl displayed a range of binding sites with different levels of affinity and proportions (%) in healthy control (CN) and Parkinson's disease (PD) brains.
• Astroglial tracers BU99008 and Deprenyl showed a highly specific (permanent) high-affinity (HA) binding site in the nanomolar range, which might be consistent across different pathologies.
• Astroglial tracers BU99008 and Deprenyl highlighted distinct tracer binding behavior, indicating that they might be targeting different subpopulations or specific states of astrocytes in CN and PD brains.
• Astroglial tracers BU99008 and Deprenyl captured prominent reactive astrogliosis at the advanced/end stages of PD, substantiated by a significant increase in intercellular adhesion molecule 1 (ICAM-1)–positive reactive astrocytes and marked changes in astrocytic morphology and processes.