Article
The endocannabinoid system and neurogenesis in health and disease.
Department of Biochemistry and Molecular Biology I, School of Biology, José Antonio Novais sn, Complutense University, 28040 Madrid, Spain.
The Neuroscientist (impact factor:
4.57).
04/2007;
13(2):109-14.
DOI:10.1177/1073858406296407
pp.109-14
Source: PubMed
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Citations (0)
- Cited In (7)
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Article: Cannabinoids and Parkinson's disease.
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ABSTRACT: Cannabinoid-based medicines have been proposed as clinically promising therapies in Parkinson's disease (PD), given the prominent modulatory function played by the cannabinoid signaling system in the basal ganglia. Supporting this pharmacological potential, the cannabinoid signaling system experiences a biphasic pattern of changes during the progression of PD. Thus, early and presymptomatic stages, characterized by neuronal malfunctioning but little evidence of neuronal death, are associated with desensitization/downregulation of CB(1) receptors. It was proposed that these losses may be part of the pathogenesis itself, since they can aggravate different cytotoxic insults which are controlled in part by cannabinoid signals, mainly excitotoxicity but also oxidative stress and glial activation. By contrast, intermediate and, in particular, advanced stages of parkinsonism characterized by a profound nigral degeneration and occurrence of major parkinsonian symptoms (e.g. bradykinesia), are associated with upregulatory responses of CB(1) receptors, possibly CB(2) receptors too, and the endocannabinoid ligands for both receptor types. This would explain the motor inhibition typical of this disease and the potential proposed for CB(1) receptor antagonists in attenuating the bradykinesia typical of PD. In addition, certain cannabinoid agonists have been proposed to serve as neuroprotective molecules in PD, given their well-demonstrated capability to reduce excitotoxicity, calcium influx, glial activation and, in particular, oxidative injury that cooperatively contribute to the degeneration of nigral neurons. However, the potential of cannabinoid-based medicines in PD have been still scarcely studied at the clinical level despite the existence of solid and promising preclinical evidence. Considering the relevance of these preclinical data, the need for finding treatments for motor symptoms that may be alternative to classic dopaminergic replacement therapy, and the lack of efficient neuroprotective strategies in PD, we believe it is of major interest to develop further studies that allow the promising expectations generated for these molecules to progress from the present preclinical evidence towards a real clinical application.CNS & neurological disorders drug targets 10/2009; 8(6):432-9. · 3.57 Impact Factor -
Article: Vulnerability Factors for the Psychiatric and Behavioral Effects of Cannabis
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ABSTRACT: Cogent evidence shows that cannabis plays a variable role on behavioral regulation and the pathophysiology of most psychiatric conditions. Accordingly, cannabis has been alternatively shown to exacerbate or ameliorate mental symptoms, depending on its composition and route of consumption, as well as specific individual and contextual characteristics. The vulnerability to the psychological effects of cannabis is influenced by a complex constellation of genetic and environmental factors. In the present article, we will review the current evidence on the pharmacological, individual and situational factors that have been documented to affect the behavioral and psychiatric effects of cannabinoids.Pharmaceuticals. 01/2010; -
Article: Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.
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ABSTRACT: Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.Proceedings of the National Academy of Sciences 06/2011; 108(27):11256-61. · 9.68 Impact Factor
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Keywords
authors address
brain injury
cell proliferation
endocannabinoid system exerts
functional endocannabinoid system
glial generation
multiple sclerosis
neural cell fate
neural progenitor cells
neuronal
pathological disorders
Recent findings
regulatory role
Research Update
various neurodegenerative diseases
