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. 2007 Aug;151(8):1272-9.
doi: 10.1038/sj.bjp.0707337. Epub 2007 Jun 25.

Cannabidiol in Vivo Blunts Beta-Amyloid Induced Neuroinflammation by Suppressing IL-1beta and iNOS Expression

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Free PMC article

Cannabidiol in Vivo Blunts Beta-Amyloid Induced Neuroinflammation by Suppressing IL-1beta and iNOS Expression

G Esposito et al. Br J Pharmacol. .
Free PMC article

Abstract

Background and purpose: Pharmacological inhibition of beta-amyloid (Abeta) induced reactive gliosis may represent a novel rationale to develop drugs able to blunt neuronal damage and slow the course of Alzheimer's disease (AD). Cannabidiol (CBD), the main non-psychotropic natural cannabinoid, exerts in vitro a combination of neuroprotective effects in different models of Abeta neurotoxicity. The present study, performed in a mouse model of AD-related neuroinflammation, was aimed at confirming in vivo the previously reported antiinflammatory properties of CBD.

Experimental approach: Mice were inoculated with human Abeta (1-42) peptide into the right dorsal hippocampus, and treated daily with vehicle or CBD (2.5 or 10 mg kg(-1), i.p.) for 7 days. mRNA for glial fibrillary acidic protein (GFAP) was assessed by in situ hybridization. Protein expression of GFAP, inducible nitric oxide synthase (iNOS) and IL-1beta was determined by immunofluorescence analysis. In addition, ELISA assay of IL-1beta level and the measurement of NO were performed in dissected and homogenized ipsilateral hippocampi, derived from vehicle and Abeta inoculated mice, in the absence or presence of CBD.

Key results: In contrast to vehicle, CBD dose-dependently and significantly inhibited GFAP mRNA and protein expression in Abeta injected animals. Moreover, under the same experimental conditions, CBD impaired iNOS and IL-1beta protein expression, and the related NO and IL-1beta release.

Conclusion and implications: The results of the present study confirm in vivo anti-inflammatory actions of CBD, emphasizing the importance of this compound as a novel promising pharmacological tool capable of attenuating Abeta evoked neuroinflammatory responses.

Figures

Figure 1
Figure 1
Effects of cannabidiol (CBD) (intraperitoneal (i.p.) treatment for 7 consecutive days) on glial fibrillary acidic protein (GFAP) mRNA in mouse hippocampus. Upper panel: Dark-field photomicrographs showing the distribution of GFAP mRNA as detected by in situ hybridization in (a) vehicle-inoculated mice (control), (b) Aβ inoculated mice, (c) Aβ inoculated and cannabidiol (CBD) (2.5 mg kg−1) i.p. treated mice, (d) Aβ inoculated and CBD (10 mg kg−1) i.p. treated mice. Lower panel: Quantification of GFAP mRNA by densitometry. Data are shown as mean±s.e.m. of five experiments. ***P<0.001 versus control; °P<0.05 and °°°P<0.001 versus Aβ inoculated mice.
Figure 2
Figure 2
Effects of cannabidiol (CBD) (intraperitoneal (i.p.) treatment for 7 consecutive days) on glial fibrillary acidic protein (GFAP) in mouse hippocampus. Upper panel:Representative photomicrographs showing GFAP immunoreactive cells in: (a) vehicle inoculated mice (control), (b) Aβ inoculated mice, (c) Aβ inoculated and CBD (2.5 mg kg−1) i.p. treated mice, (d) Aβ inoculated and CBD (10 mg kg−1) i.p. treated mice. Lower panel: Quantification of immunoreactivity expressed as the number of cells immunostained with anti-GFAP antibody. Data are shown as mean±s.e.m. of five experiments. ***P<0.001 versus control; °P<0.05, and °°°P<0.001 versus Aβ inoculated mice.
Figure 3
Figure 3
Effects of cannabidiol (CBD) (intraperitoneal (i.p.) treatment for 7 consecutive days) on inducible nitric oxide synthase (iNOS) in mouse hippocampus. Upper panel: Representative photomicrographs showing iNOS immunoreactive cells in: (a) vehicle inoculated mice (control), (b) Aβ inoculated mice, (c) Aβ inoculated and CBD (2.5 mg kg−1) i.p. treated mice, (d) Aβ inoculated and CBD (10 mg kg−1) i.p. treated mice. Lower panel: Quantification of immunoreactivity expressed as the number of cells immunostained with anti-iNOS antibody. Data are shown as mean±s.e.m. of five experiments. ***P<0.001 versus control; °P<0.05, and °°°P<0.001 versus Aβ inoculated mice.
Figure 4
Figure 4
Effects of cannabidiol (CBD) (intraperitoneal (i.p.) treatment for 7 consecutive days) on IL-1β in mouse hippocampus. Upper panel: Representative photomicrographs showing IL-1β immunoreactive cells in: (a) vehicle inoculated mice (control), (b) Aβ inoculated mice, (c) Aβ inoculated and CBD (2.5 mg kg−1) i.p. treated mice, (d) Aβ inoculated and CBD (10 mg kg−1) i.p. treated mice. Lower panel: Quantification of immunoreactivity expressed as the number of cells immunostained with anti- IL-1β antibody. Data are shown as mean±s.e.m. of five experiments. ***P<0.001 versus control; °P<0.05, and °°°P<0.001 versus Aβ inoculated mice.
Figure 5
Figure 5
Effects of cannabidiol (CBD) (2.5 or 10 mg kg−1 intraperitoneal (i.p.) for 7 consecutive days) on nitrite (NO2) level in mouse hippocampal homogenates 10 days after Aβ (1–42) (10 μg ml−1) injection into mouse hippocampi. Data are shown as mean±s.e.m. of five experiments. ***P<0.01 versus control; °P<0.05, and °°P<0.01 versus Aβ inoculated mice.
Figure 6
Figure 6
Effects of cannabidiol (CBD) (2.5 or 10 mg kg−1 intraperitoneal (i.p.) for 7 consecutive days) on IL-1β level in hippocampal homogenates 10 days after Aβ (1–42) (10 μg ml−1) injection into mouse hippocampi. Data are shown as mean±s.e.m. of five experiments. ***P<0.01 versus control; °P<0.05, and °°P<0.01 versus Aβ inoculated mice.

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