A glial endogenous cannabinoid system is upregulated in the brains of macaques with simian immunodeficiency virus-induced encephalitis.
Recent evidence supports the notion that the endocannabinoid system may play a crucial role in neuroinflammation. We explored the changes that some elements of this system exhibit in a macaque model of encephalitis induced by simian immunodeficiency virus. Our results show that profound alterations in the distribution of specific components of the endocannabinoid system occur as a consequence of the viral infection of the brain. Specifically, expression of cannabinoid receptors of the CB2 subtype was induced in the brains of infected animals, mainly in perivascular macrophages, microglial nodules, and T-lymphocytes, most likely of the CD8 subtype. In addition, the endogenous cannabinoid-degrading enzyme fatty acid amide hydrolase was overexpressed in perivascular astrocytes as well as in astrocytic processes reaching cellular infiltrates. Finally, the pattern of CB1 receptor expression was not modified in the brains of infected animals compared with that in control animals. These results resemble previous data obtained in Alzheimer's disease human tissue samples and suggest that the endocannabinoid system may participate in the development of human immunodeficiency virus-induced encephalitis, because activation of CB2 receptors expressed by immune cells is likely to reduce their antiviral response and thus could favor the CNS entry of infected monocytes.
Benito
Cristina
C
Laboratorio de Apoyo a la Investigación, Fundación Hospital Alcorcón, 28922 Madrid, Spain.
Kim
Woong-Ki
WK
Kim
Wong-Ki
WK
Chavarría
Iván
I
Hillard
Ceceila J
CJ
Mackie
Ken
K
Tolón
Rosa M
RM
Williams
Kenneth
K
Williams
Ken
K
Romero
Julián
J
D000581:Amidohydrolases / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000821:virology; D063385:Cannabinoid Receptor Modulators / Q000096:biosynthesis*; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000821:virology; D008253:Macaca mulatta; D009457:Neuroglia / Q000378:metabolism* / Q000821:virology; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus; D015854:Up-Regulation / Q000502:physiology*; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases