Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy.
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| Abstract |
Cannabinoids are neuroprotective in models of neurodegenerative dementias. Their effects are mostly mediated through CB1 and CB2 receptor-dependent modulation of excitotoxicity, inflammation, oxidative stress, and other processes. We tested the effects of Sativex®, a mixture of Δ9-tetrahydrocannabinol and cannabidiol, acting on both CB1 and CB2 receptors, in parkin-null, human tau overexpressing (PK-/-/TauVLW) mice, a model of complex frontotemporal dementia, parkinsonism, and lower motor neuron disease. The animals received Sativex®, 4.63 mg/kg, ip, daily, for one month, at six months of age, at the onset of the clinical symptoms. We evaluated the effects of Sativex® on behavior, dopamine neurotransmission, glial activation, redox state, mitochondrial activity, and deposition of abnormal proteins. PK-/-/TauVLW mice developed the neurological deficits, but those treated with Sativex® showed less abnormal behaviors related to stress, less auto and hetero-aggression, and less stereotypy. Sativex® significantly reduced the intraneuronal, MAO-related free radicals produced during dopamine metabolism in the limbic system. Sativex® also decreased gliosis in cortex and hippocampus, increased the ratio reduced/oxidized glutathione in the limbic system, reduced the levels of iNOS, and increased those of complex IV in the cerebral cortex. With regard to tau and amyloid pathology, Sativex® reduced the deposition of both in the hippocampus and cerebral cortex of PK-/-/TauVLW mice and increased autophagy. Sativex®, even after a short administration in animals with present behavioral and pathological abnormalities, improves the phenotype, the oxidative stress, and the deposition of proteins in PK-/-/TauVLW mice, a model of complex neurodegenerative disorders.
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| Authors | Maria J Casarejos, Juan Perucho, Ana Gomez, Maria P Muñoz, Marian Fernandez-Estevez, Onintza Sagredo, Javier Fernandez Ruiz, Manuel Guzman, Justo Garcia de Yebenes, Maria A Mena |
| Journal | Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 35 Issue 3 Pg. 525-39 ( 2013) ISSN: 1875-8908 [Electronic] Netherlands |
| PMID | 23478312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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