Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure
Laura Cutando, … , Rafael Maldonado, Andrés Ozaita
Laura Cutando, … , Rafael Maldonado, Andrés Ozaita
Published June 24, 2013
Citation Information: J Clin Invest. 2013;123(7):2816-2831. https://doi.org/10.1172/JCI67569.
View: Text | PDF
Research Article

Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure

Abstract

Chronic cannabis exposure can lead to cerebellar dysfunction in humans, but the neurobiological mechanisms involved remain incompletely understood. Here, we found that in mice, subchronic administration of the psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), activated cerebellar microglia and increased the expression of neuroinflammatory markers, including IL-1β. This neuroinflammatory phenotype correlated with deficits in cerebellar conditioned learning and fine motor coordination. The neuroinflammatory phenotype was readily detectable in the cerebellum of mice with global loss of the CB1 cannabinoid receptor (CB1R, Cb1–/– mice) and in mice lacking CB1R in the cerebellar parallel fibers, suggesting that CB1R downregulation in the cerebellar molecular layer plays a key role in THC-induced cerebellar deficits. Expression of CB2 cannabinoid receptor (CB2R) and Il1b mRNA was increased under neuroinflammatory conditions in activated CD11b-positive microglial cells. Furthermore, administration of the immunosuppressant minocycline or an inhibitor of IL-1β receptor signaling prevented the deficits in cerebellar function in Cb1–/– and THC-withdrawn mice. Our results suggest that cerebellar microglial activation plays a crucial role in the cerebellar deficits induced by repeated cannabis exposure.

Authors

Laura Cutando, Arnau Busquets-Garcia, Emma Puighermanal, Maria Gomis-González, José María Delgado-García, Agnès Gruart, Rafael Maldonado, Andrés Ozaita

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (5.11 MB)

Advertisement