Resident Astrocytes can Limit Injury to Developing Hippocampal Neurons upon THC Exposure.
Maria Krassnitzer, Brooke Boisvert, Johannes Beiersdorf, Tibor Harkany, Erik Keimpema
Neurochemical Research April 1, 2023 DOI: 10.1007/s11064-022-03836-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study combining transcriptome analysis, transgenic models, high resolution microscopy, and live cell imaging in vivo and in vitro Peer reviewed |
|---|---|
| Population | Hippocampal astrocytes and neurons from mice |
| Dose | > 5 µM (in vitro) |
| Duration | Long term postnatal exposure |
| Topics | Cannabis |
| Keywords | Apoptosis Astrocyte Brain development Cell proliferation |
| Key findings | Astrocytes accumulate in select hippocampal areas to protect neurons from THC-induced damage, but their own mitochondrial function is impaired. |
Abstract
Cannabis legalization prompted the dilemma if plant-derived recreational drugs can have therapeutic potential and, consequently, how to address their regulation and safe distribution. In parallel, the steady worldwide decriminalization of cannabis and the enhanced content of its main psychoactive compound Δ9-tetrahydrocannabinol (THC), exposes populations to increasing amounts of cannabis and THC across all ages. While adverse effects of cannabis during critical stages of fetal neurodevelopment are investigated, these studies center on neurons alone. Thus, a gap of knowledge exists on how intercellular interactions between neighboring cell types, particularly astrocytes and neurons, could modify THC action. Here, we combine transcriptome analysis, transgenic models, high resolution microscopy and live cell imaging to demonstrate that hippocampal astrocytes accumulate in the strata radiatum and lacunosum moleculare of the CA1 subfield, containing particularly sensitive neurons to stressors, upon long term postnatal THC exposure in vivo. As this altered distribution is not dependent on cell proliferation, we propose that resident astrocytes accumulate in select areas to protect pyramidal neurons and their neurite extensions from pathological damage. Indeed, we could recapitulate the neuroprotective effect of astrocytes in vitro, as their physical presence significantly reduced the death of primary hippocampal neurons upon THC exposure (> 5 µM). Even so, astrocytes are also affected by a reduced metabolic readiness to stressors, as reflected by a downregulation of mitochondrial proteins. Thus, we find that astrocytes exert protective functions on local neurons during THC exposure, even though their mitochondrial electron transport chain is disrupted.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 3
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- Miswiring the brain: Δ9-tetrahydrocannabinol disrupts cortical development by inducing an SCG10/stathmin-2 degradation pathway. The EMBO journal April 1, 2014