Koskinen, Maija-KreettaLaine, MikaelaAbdollahzadeh, AliGigliotta, AdrienMazzini, GiuliaJournee, SarahAlenius, VarpuTrontti, KaleviTohka, JussiHyytiä, PetriSierra, AlejandraHovatta, Iiris2023-08-232023-08-232023-09Koskinen, M-K, Laine, M, Abdollahzadeh, A, Gigliotta, A, Mazzini, G, Journee, S, Alenius, V, Trontti, K, Tohka, J, Hyytiä, P, Sierra, A & Hovatta, I 2023, 'Node of Ranvier remodeling in chronic psychosocial stress and anxiety', Neuropsychopharmacology, vol. 48, no. 10, pp. 1532-1540. https://doi.org/10.1038/s41386-023-01568-6ORCID: /0000-0002-5990-7892/work/141180509ORCID: /0000-0002-0284-1298/work/141184885ORCID: /0000-0003-2989-2527/work/141186134http://hdl.handle.net/10138/564197Differential expression of myelin-related genes and changes in myelin thickness have been demonstrated in mice after chronic psychosocial stress, a risk factor for anxiety disorders. To determine whether and how stress affects structural remodeling of nodes of Ranvier, another form of myelin plasticity, we developed a 3D reconstruction analysis of node morphology in C57BL/6NCrl and DBA/2NCrl mice. We identified strain-dependent effects of chronic social defeat stress on node morphology in the medial prefrontal cortex (mPFC) gray matter, including shortening of paranodes in C57BL/6NCrl stress-resilient and shortening of node gaps in DBA/2NCrl stress-susceptible mice compared to controls. Neuronal activity has been associated with changes in myelin thickness. To investigate whether neuronal activation is a mechanism influencing also node of Ranvier morphology, we used DREADDs to repeatedly activate the ventral hippocampus-to-mPFC pathway. We found reduced anxiety-like behavior and shortened paranodes specifically in stimulated, but not in the nearby non-stimulated axons. Altogether, our data demonstrate (1) nodal remodeling of the mPFC gray matter axons after chronic stress and (2) axon-specific regulation of paranodes in response to repeated neuronal activity in an anxiety-associated pathway. Nodal remodeling may thus contribute to aberrant circuit function associated with anxiety disorders.9engcc_byinfo:eu-repo/semantics/openAccessSocial defeatEpidemiologyGenesNeurosciencesPharmacyNeurology and psychiatryArticleopenAccessf2d0de74-9012-4295-8c8e-a69726d6a2693694914885150722367000954617300001