In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease.

By A. Gerhard, N. Pavese, G. Hotton, Federico E. Turkheimer, Meltem Es, Alexander Hammers, K. Eggert, W. Oertel, R. Banati, D. Brooks. Neurobiology of Disease, 2006

1,107 citations recorded by the source corpus.

Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/d188963f0e65b4086948dbbee7dc667807017e84

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. P. Jenner
2. S. Duty
3. M. Block
4. Jau-Shyong Hong
5. Yuanyuan Tang
6. M. Goldberg
7. Sangram S. Sisodia
8. W. Le

In Neurology

1. S. Duty
2. Marco Prinz
3. M. Block
4. P. Jenner
5. R. Ransohoff
6. Josef Priller
7. M. Tansey
8. M. Goldberg

Citations in the corpus

• Neuroinflammation in Parkinson’s disease and its potential as therapeutic target (2015, neutral): “in various regions of PD brain [13, 14].”
• Microglia-mediated neurotoxicity: uncovering the molecular mechanisms (2007, background): “In patients with Parkinson's disease, microglial activation imaged by PET was increased in the pons, basal ganglia and cortical regions (frontal and temporal”
• The Role of Oxidative Stress in Parkinson’s Disease (2013, neutral): “the brain and cerebrospinal fluid [29, 173–175].”
• Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease (2011, result): “…microglial activation seen in both the SNpc and striatum following rotenone infusion (Sherer et al., 2003b) is consistent with the inflammatory features found in idiopathic PD (Gerhard et al., 2006; Whitton, 2007; Tansey and Goldberg, 2010), lending support to the construct validity of this model.”
• Heterogeneity of CNS myeloid cells and their roles in neurodegeneration (2011, methodology): “Positron emission tomography studies using the [11C](R)-PK11195 marker of peripheral benzodiazepine binding sites revealed microglial activation in pons, basal ganglia, and frontal and temporal cortical regions of individuals with Parkinson's disease, starting early in the disease process without si”
• Toll-like receptor 4 is required for α-synuclein dependent activation of microglia and astroglia (2013, background): “a-Synucleinopathies (ASP), including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by a-synuclein (AS) positive cytoplasmic inclusions in neuronal and glial cells.”
• Neuroinflammation in Parkinson’s disease: its role in neuronal death and implications for therapeutic intervention (2009, background): “Specifically, direct nigral administration of LPS into the substantia nigra of α-synuclein (SYN)-null mice and the same mice engineered to overexpress human SYN or mutant SYN resulted in similar inflammatory reactions.”
• Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases (2015, background): “The molecular and clinical evidences from postmortem analysis and positron emission tomography (PET) imaging have shown an increase of microglial activation and an increasing accumulated inflammatory mediators during the pathogenesis of neurodegenerative diseases [5–7].”
• Mechanisms Underlying Inflammation in Neurodegeneration (2010, neutral): “Additional studies are needed to validate the specificity of this imaging approach, but these findings are suggestive of increased glial activation in PD patients (Gerhard et al., 2006).”
• Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023, background): “214 Microglia in the SN of PD patients showed a higher proportion of amoeboid morphology, which is indicative of a reactive state.”