The effect of cannabinoid treatment on reactive human-induced pluripotent stem cell-derived astrocytes

There is growing evidence that inflammation plays a role in neurodegenerative diseases, including Alzheimer’s. Astrocytes and microglia are thought to play a central role in neuronal dysfunction and/or death. This study utilises a human model of inflammation which involves differentiating astrocytes from human-induced pluripotent stem cells (iPSC), followed by stimulation with microglial-secreted factor tumour necrosis factor-alpha (TNFα). This stimulation causes the astrocytes to take on a reactive phenotype which permits the assessment of possible neuroprotective candidates.

One family of potential candidates are cannabinoids derived from the hemp plant Cannabis sativa L. (C. sativa). The two major plant-derived cannabinoids are the euphoric compound Δ9-tetrahydrocannabinol (THC) and non-euphoric cannabidiol (CBD), both of which were utilised in this study.

The iPSC-derived astrocytes were stimulated with TNFα to induce reactivity and treated with CBD+/- THC to assess their potential role in attenuating pro-inflammatory states in astrocytes. The astrocyte reactivity profile was examined via ELISA. Alamar Blue​ and LDH cytotoxicity assays were also performed to assess cell viability. qPCR analysis was conducted to assess the potential receptors involved. This is an ongoing study, but early results will be presented. So far, our data suggest that the treatment with cannabinoids does not affect astrocyte viability and we anticipate that when administered with an inflammatory signal (TNFα), it can downregulate astrocyte reactivity. qPCR analysis revealed that in reactive astrocytes, the genes encoding for the CB1, PPARα and PPARγ receptors are significantly downregulated, regardless of treatment with CBD.

 

MissingLinkText

Conflict of Interest

The authors declare no conflict of interest.

Publication History

Article published online:
16 November 2023