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Research ArticleNEUROPHARMACOLOGY

Opposing Control of Cannabinoid Receptor Stimulation on Amyloid-β-Induced Reactive Gliosis: In Vitro and in Vivo Evidence

Giuseppe Esposito, Teresa Iuvone, Claudia Savani, Caterina Scuderi, Daniele De Filippis, Michele Papa, Vincenzo Di Marzo and Luca Steardo
Journal of Pharmacology and Experimental Therapeutics September 2007, 322 (3) 1144-1152; DOI: https://doi.org/10.1124/jpet.107.121566
Giuseppe Esposito
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Teresa Iuvone
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Claudia Savani
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Caterina Scuderi
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Daniele De Filippis
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Michele Papa
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Vincenzo Di Marzo
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Luca Steardo
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Abstract

Beside cytotoxic mechanisms impacting on neurons, amyloid β (Aβ)-induced astroglial activation is operative in Alzheimer's disease brain, suggesting that persistent inflammatory response may have a role in the illness and that positive results may be achieved by curbing the astroglial reaction. Because the role of the endocannabinoid system could represent a promising field of research, the present study conducted in vitro and in vivo experiments to assess this system. C6 rat astroglioma cells were challenged with 1 μg/ml Aβ 1-42 in the presence or absence of selective agonists and antagonists of cannabinoid (CB)1 and CB2 receptors. Furthermore, rats were inoculated into the frontal cortex with 30 ng of Aβ 1-42 and were i.p. administered with 5 mg/kg of the same substances. Immunohistochemical and biochemical findings revealed that selective agonism at CB1 and antagonism at CB2 receptors was able to blunt Aβ-induced reactive astrogliosis with subsequent overexpression of glial fibrillary acidic protein and S100B protein. Moreover, Aβ provoked down-regulation of CB1 receptors together with a reduction of anandamide concentration, whereas CB2 receptors were up-regulated and 2-arachidonoyl glycerol concentration was increased. Finally, to our knowledge, the current study is the first showing that interactions at cannabinoid receptors result in a dual regulation of Aβ-induced reactive astrogliosis. The data support the assumption that compounds able to selectively block CB2 receptors may have therapeutic potential in controlling Aβ-related pathology, due to their beneficial effects devoid of psychotropic consequences.

Footnotes

  • This work was supported by Cofin Ministero dell'Università e della Ricerca Scientifica e Tecnologica 2004 (to L.S.).

  • G.E. and T.I. equally contributed to this work.

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.107.121566.

  • ABBREVIATIONS: AD, Alzheimer's disease; SP, senile plaque(s); 2-AG, 2-arachidonoyl glycerol; CB, cannabinoid receptor type; ECS, endocannabinoid system; Aβ, amyloid-β; ACEA, arachidonyl-2′-chloroethylamide; JWH-015, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone; SR141716A, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide hydrochloride; SR144528, N-((1S)-endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide); RT-PCR, reverse transcription-polymerase chain reaction; OD, optical density; PBS, phosphate-buffered saline; GFAP, glial fibrillary acidic protein; AEA, anandamide; PEA, palmitoylethanolamide; ctrl, control; WIN 55,212, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de)-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone.

  • Received February 15, 2007.
  • Accepted May 31, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 384 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 384, Issue 2
1 Feb 2023
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Research ArticleNEUROPHARMACOLOGY

Opposing Control of Cannabinoid Receptor Stimulation on Amyloid-β-Induced Reactive Gliosis: In Vitro and in Vivo Evidence

Giuseppe Esposito, Teresa Iuvone, Claudia Savani, Caterina Scuderi, Daniele De Filippis, Michele Papa, Vincenzo Di Marzo and Luca Steardo
Journal of Pharmacology and Experimental Therapeutics September 1, 2007, 322 (3) 1144-1152; DOI: https://doi.org/10.1124/jpet.107.121566

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Research ArticleNEUROPHARMACOLOGY

Opposing Control of Cannabinoid Receptor Stimulation on Amyloid-β-Induced Reactive Gliosis: In Vitro and in Vivo Evidence

Giuseppe Esposito, Teresa Iuvone, Claudia Savani, Caterina Scuderi, Daniele De Filippis, Michele Papa, Vincenzo Di Marzo and Luca Steardo
Journal of Pharmacology and Experimental Therapeutics September 1, 2007, 322 (3) 1144-1152; DOI: https://doi.org/10.1124/jpet.107.121566
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