Related Experiment Video
Updated: Jun 24, 2026
Autoradiography as a Simple and Powerful Method for Visualization and Characterization of Pharmacological Targets
Published on: March 12, 2019
Autoradiographical imaging of PPARgamma agonist effects on PBR/TSPO binding in TASTPM mice
Jennifer C Roberts1, Sarah L Friel, Shilina Roman
1Neuroscience Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK.
Abstract:
Chronic inflammation is known to occur in the brains of Alzheimer's Disease (AD) patients, including the presence of activated microglia close to amyloid plaques. We utilised real time autoradiography and immunohistochemistry to investigate microglial activation and the potential anti-inflammatory effects of PPARgamma agonists in the Thy-1 APP695swe/Thy-1 PS-1.M146V (TASTPM) overexpressing transgenic mouse model of AD. An age dependent increase in specific [3H](R)-PK11195 binding to peripheral benzodiazepine receptors (PBR)/translocator protein (18 kDa) (TSPO) was observed in the cortex of TASTPM mice compared to wild type mice, indicative of microglial activation. This was consistent with immunohistochemical data showing age-dependent increases in CD68 immunoreactivity co-localised with amyloid beta (Abeta) deposits. In 10 month old TASTPM mice, pioglitazone (20 mg/kg) and ciglitazone (50 mg/kg) significantly reduced [3H](R)-PK11195 and [3H]DPA-713 binding in cortex and hippocampus, indicative of reduced microglial activation. In AD brain, significant [3H](R)-PK11195 and [3H]DPA-713 binding was observed across all stages of the disease. These results support the use of PBR/TSPO autoradiography in TASTPM mice as a functional readout of microglial activation to assess anti-inflammatory drugs prior to evaluation in AD patients.
Insights
PPARgamma agonists reduce microglial activation in an Alzheimer's Disease (AD) mouse model. This study highlights PBR/TSPO autoradiography as a tool for assessing anti-inflammatory drugs for AD treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Alzheimer's Disease (AD) is characterized by chronic neuroinflammation, involving activated microglia near amyloid plaques.
- Microglial activation is a key pathological feature in AD brains, contributing to disease progression.
Purpose of the Study:
- To investigate microglial activation in a transgenic mouse model of AD (TASTPM mice).
- To evaluate the anti-inflammatory effects of PPARgamma agonists on microglial activation in this model.
Main Methods:
- Utilized real-time autoradiography with [3H](R)-PK11195 and [3H]DPA-713 to measure peripheral benzodiazepine receptor (PBR)/translocator protein (18 kDa) (TSPO) binding.
- Employed immunohistochemistry to assess CD68 immunoreactivity and amyloid beta (Abeta) co-localization.
- Administered PPARgamma agonists (pioglitazone and ciglitazone) to TASTPM mice.
Main Results:
- Observed an age-dependent increase in PBR/TSPO binding in TASTPM mice, indicating microglial activation.
- Found age-dependent increases in CD68 immunoreactivity co-localized with Abeta deposits.
- Pioglitazone and ciglitazone significantly reduced PBR/TSPO binding, suggesting reduced microglial activation in TASTPM mice.
Conclusions:
- PPARgamma agonists demonstrate anti-inflammatory effects by reducing microglial activation in the TASTPM AD mouse model.
- PBR/TSPO autoradiography in TASTPM mice serves as a valid functional readout for assessing anti-inflammatory drug efficacy in AD.
