Endogenous retroviruses are associated with hippocampus-based memory impairment

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Abstract: Retrotransposons compose a staggering 40% of the mammalian genome. Among them, endogenous retroviruses (ERV) represent sequences that closely resemble the proviruses created from exogenous retroviral infection. ERVs make up 8 to 10% of human and mouse genomes and range from evolutionarily ancient sequences to recent acquisitions. Studies in Drosophila have provided a causal link between genomic retroviral elements and cognitive decline; however, in mammals, the role of ERVs in learning and memory remains unclear. Here we studied 2 independent murine models for ERV activation: muMT strain (lacking B cells and antibody production) and intracerebroventricular injection of streptozotocin (ICVI-STZ). We conducted behavioral assessments (contextual fear memory and spatial learning), as well as gene and protein analysis (RNA sequencing, PCR, immunohistochemistry, and western blot assays). Mice lacking mitochondrial antiviral-signaling protein (MAVS) and mice lacking stimulator of IFN genes protein (STING), 2 downstream sensors of ERV activation, provided confirmation of ERV impact. We found that muMT mice and ICVI-STZ mice induced hippocampal ERV activation, as shown by increased gene and protein expression of the Gag sequence of the transposable element intracisternal A-particle. ERV activation was accompanied by significant hippocampus-related memory impairment in both models. Notably, the deficiency of the MAVS pathway was protective against ICVI-STZ–induced cognitive pathology. Overall, our results demonstrate that ERV activation is associated with cognitive impairment in mice. Moreover, they provide a molecular target for strategies aimed at attenuating retroviral element sensing, via MAVS, to treat dementia and neuropsychiatric disorders

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Proceedings of the National Academy of Sciences of the United States of America. - 116, 51 (2019) , 25982-25990, ISSN: 1091-6490

Schlagwort
Endogene Retroviren
Hippocampus
Kognitive Störung
Entzündung

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2020
Urheber
Sankowski, Roman
Strohl, Joshua J.
Huerta, Tomás S.
Nasiri, Elham
Mazzarello, Andrea N.
D’Abramo, Cristina
Cheng, Kai Fan
Staszewski, Ori
Prinz, Marco
Huerta, Patricio T.
Al-Abed, Yousef

DOI
10.1073/pnas.1822164116
URN
urn:nbn:de:bsz:25-freidok-1545524
Rechteinformation
Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:49 MESZ

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Entstanden

  • 2020

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