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Analysis of institutional authors

Puigdellívol MAuthorBrito VAuthorAlberch JAuthorGines SCorresponding Author

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January 8, 2018
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Cdk5 Contributes to Huntington’s Disease Learning and Memory Deficits via Modulation of Brain Region-Specific Substrates

Publicated to: Molecular Neurobiology. 55 (8): 6250-6268 - 2018-08-01 55(8), DOI: 10.1007/s12035-017-0828-4

Authors: Alvarez-Periel, Elena; Puigdellivol, Mar; Brito, Veronica; Plattner, Florian; Bibb, James A; Alberch, Jordi; Gines, Silvia

Affiliations

Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain - Author
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain - Author
Univ Alabama Birmingham, Med Ctr, UAB Comprehens Canc Ctr, Dept Surg Neurobiol & Neurol, Birmingham, AL 35294 USA - Author
Univ Barcelona, Inst Neurociencies, Fac Med, Dept Biomed, Barcelona, Spain - Author
Univ Texas Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX USA - Author
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Abstract

Cognitive deficits are a major hallmark of Huntington's disease (HD) with a great impact on the quality of patient's life. Gaining a better understanding of the molecular mechanisms underlying learning and memory impairments in HD is, therefore, of critical importance. Cdk5 is a proline-directed Ser/Thr kinase involved in the regulation of synaptic plasticity and memory processes that has been associated with several neurodegenerative disorders. In this study, we aim to investigate the role of Cdk5 in learning and memory impairments in HD using a novel animal model that expresses mutant huntingtin (mHtt) and has genetically reduced Cdk5 levels. Genetic reduction of Cdk5 in mHtt knock-in mice attenuated both corticostriatal learning deficits as well as hippocampal-dependent memory decline. Moreover, the molecular mechanisms by which Cdk5 counteracts the mHtt-induced learning and memory impairments appeared to be differentially regulated in a brain region-specific manner. While the corticostriatal learning deficits are attenuated through compensatory regulation of NR2B surface levels, the rescue of hippocampal-dependent memory was likely due to restoration of hippocampal dendritic spine density along with an increase in Rac1 activity. This work identifies Cdk5 as a critical contributor to mHtt-induced learning and memory deficits. Furthermore, we show that the Cdk5 downstream targets involved in memory and learning decline differ depending on the brain region analyzed suggesting that distinct Cdk5 effectors could be involved in cognitive impairments in HD.

Keywords

cdk5cognitioncognitive dysfunctiondendritic spine pathologydendritic spineshuntingtinmouse modelneuroprotectionnmda receptor traffickingnr2bp35phosphorylationrac1rolessynaptic plasticityAnimalsBrainCdk5Cdk5 protein, mouseCognitionCyclin-dependent kinase 5Cyclin-dependent kinase-5Dendritic spinesGene knock-in techniquesHuntingtinHuntingtin proteinHuntington diseaseLearningMemory disordersMice, inbred c57blMotor activityNeostriatumNr2bNr2b nmda receptorOrgan specificityPhosphorylationPhosphotyrosineProtein subunitsRac1Rac1 gtp-binding proteinReceptors, n-methyl-d-aspartateSrc-family kinasesSubstrate specificity

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, 2018, it was in position 57/267, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-06:

  • WoS: 21
  • Scopus: 6
  • Europe PMC: 16

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 2025-12-06:

  • 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: 47.
  • 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: 46 (PlumX).

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

    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: United States of America.

    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 (Alvarez-Periel E) and Last Author (Ginés Padrós, Silvia).

    the author responsible for correspondence tasks has been Ginés Padrós, Silvia.