Striatal Cannabinoid CB1 Receptor mRNA Expression Is Decreased in the Reserpine-Treated Rat Model of Parkinson's Disease

Silverdale, Monty; McGuire, Stephen A.; McInnes, Angus; Crossman, Alan R.; Brotchie, Jonathan M.

doi:10.1006/exnr.2001.7649

Cited by 76 publications

(48 citation statements)

References 37 publications

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“…The exact mechanisms involved in their neuroprotectant effects remain unclear but involve both CB 1 receptor-independent (antioxidant) and -dependent mechanisms (inhibition of Ca 2ϩ influx, reduced glutamate release and excitotoxicity, vasodilatation, increased NGF production and neurotrophic support, and hypothermia). Parkinson's disease (Silverdale et al, 2001). Moreover, Denovan-Wright and Robertson (2000) found that the decrease in CB 1 mRNA occurred before the onset of the motor-related Huntington's disease-like symptoms in mice and preceded neural degeneration, suggesting that abnormalities in cannabinoid signaling play a significant pathogenetic role.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy

Zhang

Hong²,

Stone

et al. 2007

J Pharmacol Exp Ther

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A clearer understanding of the mechanisms underlying the development and progression of diabetic neuropathy is likely to indicate new directions for the treatment of this complication of diabetes. In the present study we investigated the expression of cannabinoid CB 1 receptors in models of diabetic neuropathy. PC12 cells were differentiated into a neuronal phenotype with nerve growth factor (NGF) (50 ng/ml) in varying concentrations of glucose (5.5-50 mM). CB 1 receptor expression was studied at the mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR) and at the protein level via immunohistochemical and Western blot analysis. CB 1 expression was also compared in dorsal root ganglia (DRG) removed from streptozotocin-induced diabetic rats versus control animals. Total neurite length induced by NGF was reduced in cells cultured in 20 to 50 mM glucose at day 6 (P Ͻ 0.01 versus 5.5 mM; n ϭ 6). Cell viability assays conducted in parallel on day 6 confirmed that the total cell numbers were not significantly different among the various glucose concentrations (P ϭ 0.86; n ϭ 12). RT-PCR, immunohistochemical, and Western blot analysis all revealed down-regulation of the CB 1 receptor in cells treated with high glucose (P Ͻ 0.05; n ϭ 4 -5 for each), and in DRG removed from diabetic rats compared with controls (P Ͻ 0.01; n ϭ 5 for immunohistochemistry, and n ϭ 3 for Western blot). These results suggest that high glucose concentrations are associated with decreased expression of CB 1 receptors in nerve cells. Given the neuroprotective effect of cannabinoids, a decline in CB 1 receptor expression may contribute to the neurodegenerative process observed in diabetes.

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Section: Discussionmentioning

confidence: 99%

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy

Zhang

Hong²,

Stone

et al. 2007

J Pharmacol Exp Ther

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“…The above changes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated marmosets and 6-hydroxydopamine-lesioned rats were reversible by chronic Ldopa treatment, which indicates that the similar changes observed in PD patients were unlikely to have been induced by the replacement therapy (LastresBecker et al, 2001a;Maccarrone et al, 2003). There is broad agreement that the endocannabinoid system becomes overactive in the basal ganglia in PD (reviewed in Brotchie, 2003), although some studies report a reduction (Silverdale et al, 2001) or no change in CB 1 receptor expression (Herkenham et al, 1991a) or a dependence on L-DOPA cotreatment of the increased CB 1 receptor expression in the basal ganglia of animals with experimental PD (Zeng et al, 1999).…”

Section: Movement Disorders (Basal Ganglia Disorders)mentioning

confidence: 99%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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“…By contrast, CB 1 receptor transcription was increased in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) marmoset model of PD, and the mRNA levels returned to control values upon chronic L-DOPA treatment (Lastres-Becker et al, 2001a). Decreased striatal CB 1 receptor mRNA levels were found in reserpinetreated rats, an acute neurotransmitter-depletion model of PD (Silverdale et al, 2001). In summary, there seems to be a dopamine transmission-controlled mRNA expression of the CB 1 receptor, but its functional consequences remain to be clarified.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

et al. 2003

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Endocannabinoids are thought to function as retrograde messengers, which modulate neurotransmitter release by activating presynaptic cannabinoid receptors. Anandamide and 2-arachidonoylglycerol (2-AG) are the two best studied endogenous lipids which can act as endocannabinoids. Together with the proteins responsible for their biosynthesis, inactivation and the cannabinoid receptors, these lipids constitute the endocannabinoid system. This system is proposed to be involved in various neurodegenerative diseases such as Parkinson's and Huntington's diseases as well as Multiple Sclerosis. It has been demonstrated that the endocannabinoid system can protect neurons against glutamate excitotoxicity and acute neuronal damage in both in vitro and in vivo models. In this paper we review the data concerning the involvement of the endocannabinoid system in neurodegenerative diseases in which neuronal cell death may be elicited by excitotoxicity. We focus on the biosynthesis of endocannabinoids and on their modes of action in animal models of these neurodegenerative diseases.

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Striatal Cannabinoid CB1 Receptor mRNA Expression Is Decreased in the Reserpine-Treated Rat Model of Parkinson's Disease

Cited by 76 publications

References 37 publications

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

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Striatal Cannabinoid CB1 Receptor mRNA Expression Is Decreased in the Reserpine-Treated Rat Model of Parkinson's Disease

Cited by 76 publications

References 37 publications

Expression of Cannabinoid CB1 Receptors in Models of Diabetic Neuropathy

Expression of Cannabinoid CB1 Receptors in Models of Diabetic Neuropathy

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Biosynthesis of endocannabinoids and their modes of action in neurodegenerative diseases

Contact Info

Product

Resources

About

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy

Expression of Cannabinoid CB₁ Receptors in Models of Diabetic Neuropathy