Evidence map›Paper›PMID 42373968›Full record

ArticleMolecular neurobiology2026

DEK Loss Induces Task-specific Deficits in Learning and Memory and Reprograms the Hippocampal Transcriptome in Mice.

Kaitlyn L Gardner, Taylor E Lange, Marla K Perna, Susanne I Wells, Michael T Williams, Charles V Vorhees, Marley Cox, Matia B Solomon, Lisa M Privette Vinnedge

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Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Kaitlyn L Gardner *Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Taylor E Lange *Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Marla K PernaDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Susanne I WellsDivision of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Michael T WilliamsDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Charles V VorheesDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Marley CoxDepartment of Psychology, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, USA.
Matia B SolomonDepartment of Psychology, University of Cincinnati College of Arts and Sciences, Cincinnati, OH, USA. solomomb@ucmail.uc.edu.
Lisa M Privette VinnedgeDivision of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Lisa.Privette@cchmc.org.ORCID https://orcid.org/0000-0003-2087-4920

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DEK is an estrogen-responsive chromatin-remodeling protein broadly expressed in the murine and human brain, with high expression in memory-relevant regions such as the hippocampus. Prior work from our group and others has linked DEK loss to cellular features associated with Alzheimer's disease and Alzheimer's disease-related dementias. Notably, our group has demonstrated that DEK expression declines with increasing dementia severity in women, but not in age-matched men, suggesting a sex-specific relationship between DEK loss and cognitive vulnerability. Together, these findings support a potential neuroprotective role for DEK; however, functional consequences of DEK loss in vivo were unknown. Here, we examined behavioral and molecular consequences of Dek loss using male and female constitutive knockout (cKO) mice assessed across cognitive, sensorimotor, and affective domains. Across assays, Dek cKO mice of both sexes exhibited intact locomotor activity, anxiety-related behavior, sensorimotor gating, and fear-associated memory. In contrast, female Dek cKO mice displayed selective impairments in cognitive flexibility despite preserved spatial learning and memory, a phenotype not observed in males and indicative of female-specific vulnerability following DEK loss. This sex difference, observed during Morris water maze reversal learning, suggests disruption of hippocampal-prefrontal circuitry. Guided by known sex differences in hippocampal DEK expression, transcriptomic profiling of hippocampal tissue revealed shared and sex-specific consequences of Dek deficiency, including alterations in cytoskeletal organization, neuronal signaling, chromatin regulatory mechanisms, and cellular stress pathways. Collectively, these findings demonstrate sex- and cognitive-domain-specific effects of DEK loss and support further investigation of DEK in executive function and hippocampal-prefrontal cortex-mediated cognition.

Indexed as

Chromosomal Proteins, Non-HistoneHippocampusMemoryOncogene ProteinsPoly-ADP-Ribose Binding ProteinsTranscriptomeAnimalsBehavior, AnimalDNA-Binding ProteinsFemaleMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutChromosomal Proteins, Non-HistoneDEK protein, mouseDNA-Binding ProteinsOncogene ProteinsPoly-ADP-Ribose Binding ProteinsChromatinCognitive dysfunctionCognitive flexibilityDEKHippocampusMemoryMorris Water MazeReversal learningSex differences

Identifiers

PMID42373968
PMCPMC13314828

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.