Dr Ahmad Allouche, Head of in vitro biology, presented the team’s research* during at Venusberg Neuroinflammation Meeting 2025 in Luxembourg in his poster “NEUROINFLAMMATION MODELS OF NEURODEGENERATIVE DISEASES“.
Learn more about our cutting-edge platform for target identification & drug discovery in the poster!
Authors: *Ahmad ALLOUCHE, Valentin TALLANDIER, Léane DIER, Sonia KRIDI, Julie COLIN, Nicolas VIOLLE.
Affiliation: 1 ETAP-LAB, 54500, Vandœuvre-lès-Nancy, France
Abstract:
Neuroinflammation plays a pivotal role in the pathogenesis of neurodegenerative diseases (NDDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). While inflammation is essential for brain defense, chronic neuroinflammation can lead to neuronal damage and accelerate disease progression. Understanding the relationship between neuroinflammation and disease development is crucial for developing effective therapeutic strategies.
In this study, we investigated age-related changes in glial cell reactivity following neuroinflammatory stimulation. Using young and aged wild-type mice, we analyzed the response of astrocytes and microglia after a single intracerebral injection of either vehicle or amyloid-beta oligomers (AβO), a major toxic species implicated in AD. To further investigate the underlying mechanisms of neuroinflammation and bridge the gap between animal models and human systems, we assessed AβO-induced astrocyte activation in human induced pluripotent stem cell (hiPSC)-derived astrocytes using high-throughput imaging. This approach overcomes the limitations of traditional animal models and provides a more physiologically relevant representation of human neuroinflammatory responses.
Our results showed that while the overall astrocyte population remains stable with aging, the proportion of reactive astrocytes increases significantly across multiple brain regions. Moreover, a significant expansion of microglial population was observed in aged mice, suggesting a progressive neuroinflammatory response. AβO administration exacerbates astrocyte reactivity and microglial activation in both young and aged mice, highlighting the pro-inflammatory effects of this neurotoxin. While these findings in the murine model provide valuable insights into the neuroinflammatory processes underlying AD, we extend our investigation to human-derived astrocytes to further explore the cellular response mechanisms to AβO. In hiPSC-derived astrocytes, AβO exposure triggered reactivation via the nuclear factor kappa B (NF-κB) pathway, providing a more precise understanding of the disease mechanism in human cells. Interestingly, treatment with Etanercept, a TNF-α inhibitor, attenuates astrocyte reactivation in a dose-dependent manner.
These findings highlight the impact of aging and AβO exposure on glial cell function and suggest potential therapeutic strategies targeting NF-κB pathway, a key inflammatory pathway, to mitigate astrocyte reactivation and its downstream effects in neurodegenerative diseases.
