Activation of the CB2 receptor system reverses amyloid-induced memory deficiency

Wu, Jiang; Bie, Bihua; Yang, Hui; Xu, Jijun; Brown, David L.; Naguib, Mohamed

doi:10.1016/j.neurobiolaging.2012.06.011

Cited by 146 publications

(115 citation statements)

References 66 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…2A, B). In contrast to what was previously observed at early stages of AD-like pathology in A␤PP/PS1 mice [11], 9 -THC + CBD was not able to reduce the level of soluble A␤ 42 and A␤ 40 when administered at advanced stages of the disease (Fig. 2E).…”

Section: The Combination Of δ 9 -Thc and Cbd Does Not Alter Aβ Procescontrasting

confidence: 97%

“…The endocannabinoid system is a complex network of cellular receptors and signaling molecules [7] highly expressed in brain and targeted by cannabis derivatives which, when activated, provides neuroprotection by reducing neuronal damage, neuroinflammation, and oxidative stress, as well as promoting intrinsic repair mechanisms [3]. Thus, chronic stimulation with selective synthetic agonists of CB 1 and CB 2 receptors, the most well-known cannabinoid receptors, reduces cognitive impairment and brain alterations associated with A␤ production, in at least three different animal models of AD [8][9][10][11]. Moreover, the combination of 9 -tetrahydrocannabinol ( 9 -THC) and cannabidiol (CBD), two phytocannabinoids produced by the plant Cannabis sativa, reduces the pathological phenotype in mouse models of AD and tauopathy when administered at early stages of the disease [12,13].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model

Aso

Andrés‐Benito

Ferrer

2016

JAD

View full text Add to dashboard Cite

Abstract. Previous reports have demonstrated that the combination of 9 -tetrahydrocannabinol ( 9 -THC) and cannabidiol (CBD) botanical extracts, which are the components of an already approved cannabis-based medicine, reduce the Alzheimerlike phenotype of A␤PP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in A␤PP/PS1 mice at advanced stages of the disease but are not effective in modifying the A␤ processing or in reducing the glial reactivity associated with aberrant A␤ deposition as occurs when administered at early stages of the disease. The present study also demonstrates that natural cannabinoids do not affect cognitive impairment associated with healthy aging in wild-type mice. The positive effects induced by 9 -THC and CBD in aged A␤PP/PS1 mice are associated with reduced GluR2/3 and increased levels of GABA-A Rα1 in cannabinoid-treated animals when compared with animals treated with vehicle alone.

show abstract

Section: The Combination Of δ 9 -Thc and Cbd Does Not Alter Aβ Procescontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model

Aso

Andrés‐Benito

Ferrer

2016

JAD

View full text Add to dashboard Cite

show abstract

“…The flourish of recent reports of the role of the CB 2 receptor in AD (11) and of the CB 2 receptor manipulation in mouse models of AD (13)(14)(15) suggest that the field of AD therapeutics is moving toward experimental cannabinoid interventions in humans, perhaps targeting the CB 2 receptor. Of note, each of these studies focused on amyloid models of disease, and only one study included tau outcomes (14).…”

Section: Discussionmentioning

confidence: 99%

“…A subsequent investigation with the same compound in APP/presenilin 1 (PS1) mice revealed that treatment induced cognitive improvement, as well as reduced expression of the proinflammatory cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ (14). Recently, a novel CB 2 agonist (MDA7) was shown to promote Aβ clearance, decrease IL-1β and improve memory in rats with cognitive impairment induced by bilateral microinjections of Aβ into the hippocampus (15).…”

Section: Introductionmentioning

confidence: 99%

CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease

Koppel

Vingtdeux

Marambaud

et al. 2013

Mol Med

View full text Add to dashboard Cite

The endocannabinoid CB 2 receptor system has been implicated in the neuropathology of Alzheimer's disease (AD). In order to investigate the impact of the CB 2 receptor system on AD pathology, a colony of mice with a deleted CB 2 receptor gene, CNR2, was established on a transgenic human mutant APP background for pathological comparison with CB 2 receptor-sufficient transgenic mice. J20 APP (PDGFB-APPSwInd) mice were bred over two generations with CNR2 -/-(Cnr2 tm1Dgen /J) mice to produce a colony of J20 CNR2 +/+ and J20 CNR2 -/-mice. Seventeen J20 CNR2 +/+ mice (12 females, 5 males) and 16 J20 CNR2 -/-mice (11 females, 5 males) were killed at 12 months, and their brains were interrogated for AD-related pathology with both biochemistry and immunocytochemistry (ICC). In addition to amyloid-dependent endpoints such as soluble Aβ production and plaque deposition quantified with 6E10 staining, the effect of CB 2 receptor deletion on total soluble mouse tau production was assayed by using a recently developed high-sensitivity assay. Results revealed that soluble Aβ42 and plaque deposition were significantly increased in J20 CNR2 -/-mice relative to CNR2 +/+ mice. Microgliosis, quantified with ionized calcium-binding adapter molecule 1 (Iba-1) staining, did not differ between groups, whereas plaque associated microglia was more abundant in J20 CNR2 -/-mice. Total tau was significantly suppressed in J20 CNR2 -/-mice relative to J20 CNR2 +/+ mice. The results confirm the constitutive role of the CB 2 receptor system both in reducing amyloid plaque pathology in AD and also support tehpotential of cannabinoid therapies targeting CB 2 to reduce Aβ; however, the results suggest that interventions may have a divergent effect on tau pathology.

show abstract

“…CB2 deficiency was shown to affect both the ability to activate microglia and the recruitment of macrophages into the brains of AD mice (Schmöle et al, 2015). Furthermore, pharmacological studies in rodents have also suggested that CB2 plays a crucial role in AD-associated inflammatory responses (Wu et al, 2013). The CB2-deficient microglial cells showed decreased responses to stimulation with LPS/IFNg as well as reduced expression levels of proinflammatory cell surface markers (Ehrhart et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

Tang

Bao

et al. 2017

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR- 139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.

show abstract

Activation of the CB2 receptor system reverses amyloid-induced memory deficiency

Cited by 146 publications

References 66 publications

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model

Delineating the Efficacy of a Cannabis-Based Medicine at Advanced Stages of Dementia in a Murine Model

CB2 Receptor Deficiency Increases Amyloid Pathology and Alters Tau Processing in a Transgenic Mouse Model of Alzheimer’s Disease

MicroRNA-139 modulates Alzheimer’s-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

Contact Info

Product

Resources

About