Pharmacological manipulation of cannabinoid neurotransmission reduces neuroinflammation associated with normal aging

Isabelle Bardou, Nicholas DiPatrizio, Holly M. Brothers, Roxanne M. Kaercher, Kevin Baranger, Mollie Mitchem, Sarah C. Hopp, Gary L. Wenk, Yannick Marchalant

Department of Pharmacology, University of California, Irvine, USA.
Department of Psychology, Ohio State University, Columbus, USA.
NICN, Aix-Marseille University, Marseille, France.
NICN, CNRS UMR 7259, Marseille, France.

DOI: 10.4236/health.2012.429107                

Abstract

We have previously demonstrated that antagonism of glutamate NMDA receptors or activation of endocannabinoid receptors could reduce experimentally induced neuroinflammation within the hippocampus of young rats. In the current study, we investigated whether pharmacological manipulation of glutamate or endocannabinoid neurotransmission could reduce naturally-occurring neuroinflammation within the hippocampus of aged rats. We investigated whether UCM707, an inhibitor of endocannabinoid re-uptake, WIN- 55,212-2, an endocannabinoid receptor agonist, and URB597, an inhibitor of endocannabinoid catabolism, or memantine, a non-competitive, low-affinity, inhibitor of the open NMDA receptor channel, could reduce the number of MHC II-IR microglia within the hippocampus. All of the drugs, except URB597, reduced the number of reactive microglia, as compared to vehicle treated rats. The current results suggest potential pharmacological approaches that may mitigate the pathological consequences of chronic brain inflammation associated with numerous neurodegenerative diseases.

Keywords

Rats; Memantine; UCM707; Microglia; WIN-55, 212-2; URB597

Conflicts of Interest

The authors declare no conflicts of interest.

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