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Fernández Ruiz JAuthor
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Natural cannabinoids improve dopamine neurotransmission and tau and amyloid pathology in a mouse model of tauopathy

Publicated to:JOURNAL OF ALZHEIMERS DISEASE. 35 (3): 525-539 - 2013-01-01 35(3), DOI: 10.3233/JAD-130050

Authors: Casarejos MJ; Perucho J; Gomez A; Muñoz MP; Fernandez-Estevez M; Sagredo O; Fernandez Ruiz J; Guzman M; De Yebenes JG; Mena MA

Affiliations

CIBER Enfermedades Neurodegenerativas - Author
Hospital Ramón y Cajal - Author
Universidad Complutense de Madrid - Author

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 Δ -tetrahydrocannabinol and cannabidiol, acting on both CB1 and CB2 receptors, in parkin-null, human tau overexpressing (PK / Tau ) 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 /Tau 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 /Tau 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 /Tau mice, a model of complex neurodegenerative disorders. © 2013 - IOS Press and the authors. All rights reserved. ® 9 -/- VLW ® ® -/- VLW ® ® ® ® -/- VLW ® -/- VLW

Keywords
AmyloidAutophagyCannabinoidsDopamineFrontotemporal dementiaLower motor neuron diseaseParkinParkinsonismReactive oxygen speciesSativex^{\regd}Tau

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF ALZHEIMERS DISEASE due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2013, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous). Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 2.98. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 3.7 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 12.61 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-02, the following number of citations:

  • WoS: 78
  • Scopus: 105
  • OpenCitations: 99
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 177.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 177 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 26.24.
  • The number of mentions on the social network Facebook: 2 (Altmetric).
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.