{rfName}
De

Indexed in

License and use

Citations

30

Altmetrics

Grant support

Financial supports were obtained from University of Girona (MPCUdG2016/036 to XX) and the Spanish Ministry of Sciences, Innovation and Universities (through project no. SAF201788076-R and RETICS de Terapia Celular, Instituto de Salud Carlos III (RD06/0010/0006) to JA).

Analysis of institutional authors

Vidal-Sancho LAuthorFernández-García SAuthorAlberch JAuthor

Share

August 10, 2020
Publications
>
Article
No

Decreased Myocyte Enhancer Factor 2 Levels in the Hippocampus of Huntington's Disease Mice Are Related to Cognitive Dysfunction

Publicated to:Molecular Neurobiology. 57 (11): 4549-4562 - 2020-11-01 57(11), DOI: 10.1007/s12035-020-02041-x

Authors: Vidal-Sancho, L; Solés-Tarrés, I; Xifró, X; Fernández-García, S; Alberch, J

Affiliations

Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, 28031, Spain. - Author
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain - Author
Departament de Biomedicina, Institut de Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Spain. - Author
Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, 17003, Girona, Spain. xavier.xifro@udg.edu. - Author
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, 08036, Spain. - Author
New Therapeutic Targets Group, Department of Medical Science, Faculty of Medicine, University of Girona, 17003, Girona, Spain. - Author
New Therapeutic Targets Group, Department of Medical Science, Faculty of Medicine, University of Girona, 17003, Girona, Spain. xavier.xifro@udg.edu. - Author
Univ Barcelona, Fac Med, Inst Neurociencies, Dept Biomed, Barcelona 08036, Spain - Author
Univ Girona, Dept Ciencies Med, Fac Med, Girona 17003, Spain - Author
Univ Girona, Fac Med, Dept Med Sci, New Therapeut Targets Grp, Girona 17003, Spain - Author
See more

Abstract

People suffering from Huntington's disease (HD) present cognitive deficits. Hippocampal dysfunction has been involved in the HD learning and memory impairment, but proteins leading this dysregulation are not fully characterized. Here, we studied the contribution of the family of transcription factors myocyte enhancer factor 2 (MEF2) to the HD cognitive deficits. To this aim, we first analyzed MEF2 protein levels and found that they are reduced in the hippocampus of exon-1 (R6/1) and full-length (HdhQ7/Q111) mutant huntingtin (mHTT) mice at the onset of cognitive dysfunction. By the analysis of MEF2 mRNA levels and mHTT-MEF2 interaction, we discarded that reduced MEF2 levels are due to changes in the transcription or sequestration in mHTT aggregates. Interestingly, we showed in R6/1 primary hippocampal cultures that reduction of MEF2 is strongly related to a basal and non-apoptotic caspase activity. To decipher the involvement of hippocampal decreased MEF2 in memory impairment, we used the BML-210 molecule that activates MEF2 transcriptional activity by the disruption MEF2-histone deacetylase class IIa interaction. BML-210 treatment increased the number and length of neurites in R6/1 primary hippocampal cultures. Importantly, this effect was prevented by transduction of lentiviral particles containing shRNA against MEF2. Then, we demonstrated that intraperitoneal administration of BML-210 (150 mg/Kg/day) for 4 days in R6/1 mice improved cognitive performance. Finally, we observed that BML-210 treatment also promoted the activation of MEF2-dependent memory-related genes and the increase of synaptic markers in the hippocampus of R6/1 mice. Our findings point out that reduced hippocampal MEF2 is an important mediator of cognitive dysfunction in HD and suggest that MEF2 slight basal activation could be a good therapeutic option.

Keywords

ActivationAnilidesAnimalsBiomarkersCag repeatCaspase 3Caspase-3Cells, culturedCognitive dysfunctionDisease models, animalHdac4HippocampusHuntingtin proteinHuntington diseaseHuntington's diseaseHuntington’s diseaseLong-term depressionMaleMef-2Mef2Mef2 transcription factorsMemoryMemory declineMice, transgenicMutant proteinsNeuritesNeuronal plasticityNeuronal-activityProtein bindingR6/1 mouse modelRna, messengerSynapsesSynaptic plasticityTranscription factor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Neurobiology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2020, it was in position 61/273, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 1.73, which 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: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-05, the following number of citations:

  • WoS: 11
  • Scopus: 12
  • Europe PMC: 7

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 2025-07-05:

  • 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: 21.
  • 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: 30 (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: 14.15.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Vidal Rosa, Sandra) .