Cellular neuroscienceGlial expression of cannabinoid CB2 receptors and fatty acid amide hydrolase are beta amyloid–linked events in Down’s syndrome
Section snippets
Samples
Human brain cortices from three controls and seven DS patients (see Table 1) were obtained at autopsy. Control subjects had no background of neuropsychiatric disease and the full neuropathological examination performed in every case on paraffin-embedded tissue excluded any significant pathological finding. Fixation was done by immersion in 4% buffered formaldehyde; tissues were then paraffin-embedded and cut on a Leica microtome.
Immunohistochemistry
The protocol used is as described previously (Benito et al 2005,
Results
Among seven DS and three control cases analyzed, only three exhibited Aβ plaques. As expected, these samples corresponded to DS donors of adult age (34, 48 and 51 years old). Additionally, the amount of observed Aβ deposits increased with age, being maximum in the cortex of the 51-year-old tissue samples, in which a significant portion of the cerebral gray matter (Fig. 1) was occupied by these pathological structures (with more than 20 plaques/cm2 of tissue, see Table 1). These samples also
Discussion
The most relevant finding reported in this study is the direct link connecting Aβ deposition with the increase of cannabinoid CB2 and FAAH expression on glial cells. The known association of Aβ deposition and neuroinflammation (Griffin et al., 1995) allows our data to corroborate and expand previous reports from our group and others indicating that the ECS undergoes dramatic changes in response to neuroinflammatory conditions (Benito et al 2003, Benito et al 2005, Benito et al 2007,
Conclusion
In summary, the expression of CB2 receptors and FAAH is induced in glial cells surrounding Aβ plaques in DS, in concordance with previous observations in AD. Microgial CB2 and/or astroglial FAAH may participate in the pathogenesis of Aβ-induced inflammation as well as constitute novel therapeutic targets.
Acknowledgments
Authors are indebted to Ms. Sue A. Woodward for excellent technical help and to Ms. Julia Molina for administrative support. This work was financed by grants from the Ministerio de Educación y Ciencia (SAF 2004/00237, J.R.), Comunidad Autónoma de Madrid (S-SAL/0261/2006, J.R.), and National Institutes of Health (AG12411 and HD37989, W.S.T.G.). The authors declare there are no actual or potential conflicts of interest. Human samples were obtained according to Institutional Guidelines (University
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