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Updated: Jul 19, 2026
Strategies for Study of Neuroprotection from Cold-preconditioning
Published on: September 2, 2010
Purinergic exposure induces epigenomic and transcriptomic-mediated preconditioning resembling epilepsy-associated
Ricardo Martins-Ferreira1,2,3,4, Josep Calafell-Segura1, João Chaves3,4,5
1Epigenetics and Immune Disease Group, Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Barcelona, Spain.
Abstract:
Microglia play a crucial role in a range of neuropathologies through exacerbated activation. Microglial inflammatory responses can be influenced by prior exposures to noxious stimuli, like increased levels of extracellular adenosine and ATP. These are characteristic of brain insults like epileptic seizures and could potentially shape subsequent responses through epigenetic regulation. We investigated DNA methylation and expression changes in human microglia-like cells differentiated from monocytes following ATP-mediated preconditioning. We demonstrate that microglia-like cells display homeostatic microglial features, shown by surface markers, transcriptome, and DNA methylome. After exposure to ATP, TLR-mediated activation leads to an exacerbated pro-inflammatory response. These changes are accompanied by methylation and transcriptional reprogramming associated with enhanced immune-related functions. The reprogramming associated with ATP-mediated preconditioning leads to profiles found in microglial subsets linked to epilepsy. Purine-driven microglia immune preconditioning drives epigenetic and transcriptional changes that could contribute to altered functions of microglia during seizure development and progression.
Insights
Prior exposure to adenosine triphosphate (ATP) epigenetically reprograms microglia, exacerbating inflammatory responses. This purine-driven immune preconditioning in microglia may contribute to altered functions during epilepsy development and progression.
Area of Science:
- Neuroscience
- Immunology
- Epigenetics
Background:
- Microglia, the brain's immune cells, are implicated in neuropathologies due to overactivation.
- Extracellular adenosine and ATP, elevated during brain insults like seizures, can influence microglial inflammatory responses.
- Epigenetic mechanisms, such as DNA methylation, may mediate these altered microglial responses.
Purpose of the Study:
- To investigate the impact of ATP-mediated preconditioning on DNA methylation and gene expression in human microglia-like cells.
- To determine if ATP preconditioning alters microglial responses to subsequent inflammatory stimuli.
- To explore the potential role of these epigenetic changes in microglial subsets associated with epilepsy.
Main Methods:
- Differentiated human monocytes into microglia-like cells.
- Applied ATP preconditioning to these cells.
- Analyzed surface markers, transcriptome, and DNA methylome.
- Assessed microglial responses following Toll-like receptor (TLR)-mediated activation post-preconditioning.
Main Results:
- Microglia-like cells exhibited homeostatic microglial features.
- ATP preconditioning led to an exacerbated pro-inflammatory response upon TLR activation.
- These changes were associated with significant DNA methylation and transcriptional reprogramming, enhancing immune-related functions.
- The altered profiles resembled those found in microglial subsets linked to epilepsy.
Conclusions:
- Purine-driven immune preconditioning in microglia induces epigenetic and transcriptional modifications.
- These changes can lead to enhanced inflammatory responses and altered microglial functions.
- This reprogramming may contribute to the role of microglia in seizure development and progression.
