Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats.

Department of Psychology, Psychology Building, Ohio State University, Columbus, OH 43210, USA.
Neurobiology of aging (Impact Factor: 4.85). 07/2007; 29(12):1894-901. DOI: 10.1016/j.neurobiolaging.2007.04.028
Source: PubMed

ABSTRACT The number of activated microglia increase during normal aging. Stimulation of endocannabinoid receptors can reduce the number of activated microglia, particularly in the hippocampus, of young rats infused chronically with lipopolysaccharide (LPS). In the current study we demonstrate that endocannabinoid receptor stimulation by administration of WIN-55212-2 (2mg/kg day) can reduce the number of activated microglia in hippocampus of aged rats and attenuate the spatial memory impairment in the water pool task. Our results suggest that the action of WIN-55212-2 does not depend upon a direct effect upon microglia or astrocytes but is dependent upon stimulation of neuronal cannabinoid receptors. Aging significantly reduced cannabinoid type 1 receptor binding but had no effect on cannabinoid receptor protein levels. Stimulation of cannabinoid receptors may provide clinical benefits in age-related diseases that are associated with brain inflammation, such as Alzheimer's disease.

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    ABSTRACT: The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain.
    Journal of Neuroinflammation 04/2015; 12. DOI:10.1186/s12974-015-0282-z · 4.90 Impact Factor
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    ABSTRACT: The purpose of the experiments was to explore the role of the endocannabinoid system, through cannabinoid (CB) receptor ligands, nicotine and scopolamine, in the depression-related responses using the forced swimming test (FST) in mice. Our results revealed that acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, caused antidepressant-like effect in the FST, while AM 251 (0.25-3mg/kg), a CB1 receptor antagonist, did not provoke any effect in this test. Moreover, acute administration of both CB2 receptor agonist, JWH 133 (0.5 and 1mg/kg) and CB2 receptor antagonist, AM 630 (0.5mg/kg), exhibited antidepressant action. Antidepressant effects of oleamide and JWH 133 were attenuated by acute injection of both non-effective dose of AM 251, as well as AM 630. Among the all CB compounds used, only the combination of non-effective dose of oleamide (2.5mg/kg) with non-effective dose of nicotine (0.5mg/kg) caused an antidepressant effect. However, none of the CB receptor ligands, had influence on the antidepressant effects provoked by nicotine (0.2mg/kg) injection. In turn, the combination of non-effective dose of oleamide (2.5mg/kg); JWH (2mg/kg) or AM 630 (2mg/kg), but not of AM 251 (0.25mg/kg), with non-effective dose of scopolamine (0.1mg/kg), exhibited antidepressant properties. Indeed, all of the CB compounds used, intensified the antidepressant-like effects induced by an acute injection of scopolamine (0.3mg/kg). Our results provide clear evidence that the endocannabinoid system participates in the depression-related behavior and through interactions with cholinergic system modulate these kind of responses. Copyright © 2015. Published by Elsevier B.V.
    Behavioural Brain Research 02/2015; 284. DOI:10.1016/j.bbr.2015.01.051 · 3.39 Impact Factor


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May 28, 2014