Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encepha
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ORIGINAL RESEARCH
Prenatal Stress Impairs Spinal Cord Oligodendrocyte Maturation via BDNF Signaling in the Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis Maria Serena Paladini1 · Davide Marangon2 · Andrea C. Rossetti1 · Alice Guidi1 · Giusy T. Coppolino2 · Camilla Negri2 · Vittoria Spero1 · Maria Pia Abbracchio2 · Davide Lecca2 · Raffaella Molteni1 Received: 12 July 2020 / Accepted: 17 November 2020 © The Author(s) 2020
Abstract One of the most substantial and established environmental risk factors for neurological and psychiatric disorders is stress exposure, whose detrimental consequences hinge on several variables including time. In this regard the gestational period is known to present an intrinsic vulnerability to environmental insults and thus stressful events during pregnancy can lead to severe consequences on the offspring’s brain development with long-term repercussions throughout adulthood. On this basis, we investigated the long-lasting impact of prenatal stress exposure on the susceptibility to the experimental autoimmune encephalomyelitis (EAE), a well-established murine model of multiple sclerosis. Although stress is considered a triggering factor for this chronic, progressive, autoimmune disease, little is known about the underlying mechanisms. To this end, EAE was induced by immunization with MOG35-55/CFA and pertussis toxin administration in adult female C57BL/6 mice born from control or stressed dams exposed to restraint stress during the last days of gestation. Our results demonstrate that gestational stress induces a marked increase in the severity of EAE symptoms in adulthood. Further, we highlight an altered maturation of oligodendrocytes in the spinal cord of prenatally stressed EAE mice, as indicated by the higher levels of GPR17, a marker of immature oligodendrocyte precursor cells. These behavioral and molecular alterations are paralleled by changes in the expression and signaling of the neurotrophin BDNF, an important mediator of neural plasticity that may contribute to stress-induced impaired remyelination. Since several already marketed drugs are able to modulate BDNF levels, these results pave the way to the possibility of repositioning these drugs in multiple sclerosis. Keywords Prenatal stress · Experimental autoimmune encephalomyelitis · Multiple sclerosis · Brain-derived neurotrophic factor · Myelination · Spinal cord
The present work is part of the doctoral dissertation of the first author MSP, that can accessed at the following link: http://hdl. handle.net/2434/694054 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-020-01014-x) contains supplementary material, which is available to authorized users. * Raffaella Molteni [email protected] 1
Department of Medical Biotechnology and Translational Medicine, University of Milan, via Vanvitelli 32, 20129 Milan, Italy
Department of Pharmaceutical Sciences, University of Milan, via Balzaretti 9, 20133 Milan, Italy
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