PMID- 31557646 OWN - NLM STAT- MEDLINE DCOM- 20200302 LR - 20231020 IS - 1934-8800 (Electronic) IS - 0163-6383 (Print) IS - 0163-6383 (Linking) VI - 57 DP - 2019 Nov TI - DNA methylation and behavioral changes induced by neonatal spinal transection. PG - 101381 LID - S0163-6383(19)30060-8 [pii] LID - 10.1016/j.infbeh.2019.101381 [doi] AB - Although the importance of epigenetic mechanisms in behavioral development has been gaining attention in recent years, research has largely focused on the brain. To our knowledge, no studies to date have investigated epigenetic changes in the developing spinal cord to determine the dynamic manner in which the spinal epigenome may respond to environmental input during behavioral development. Animal studies demonstrate that spinal cord plasticity is heightened during early development, is somewhat preserved following neonatal transection, and that spinal injured animals are responsive to sensory feedback. Because epigenetic alterations have been implicated in brain plasticity and are highly responsive to experience, these alterations are promising candidates for molecular substrates of spinal plasticity as well. Thus, the current study investigated behavioral changes in the development of weight-bearing locomotion and epigenetic modifications in the spinal cord of infant rats following a neonatal low-thoracic spinal transection or sham surgery on postnatal day (P)1. Specifically, global levels of methylation and methylation status of the brain-derived neurotrophic factor (Bdnf) gene, a neurotrophin heavily involved in both CNS and behavioral plasticity, particularly in development, were examined in lumbar tissue harvested on P10 from sham and spinal-transected subjects. Behavioral results demonstrate that compared to shams, spinal-transected subjects exhibit significantly reduced partial-weight bearing hindlimb activity. Molecular data demonstrate group differences in global lumbar methylation levels as well as exon-specific group differences in Bdnf methylation. This study represents an initial step toward understanding the relationship between epigenetic mechanisms and plasticity associated with spinal cord and locomotor development. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Doherty, Tiffany S AU - Doherty TS AD - Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, 19716, United States. FAU - Bozeman, Aimee L AU - Bozeman AL AD - Department of Psychology, Idaho State University, Pocatello, ID, 83209, United States. FAU - Roth, Tania L AU - Roth TL AD - Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, 19716, United States. FAU - Brumley, Michele R AU - Brumley MR AD - Department of Psychology, Idaho State University, Pocatello, ID, 83209, United States. Electronic address: brummich@isu.edu. LA - eng GR - P20 GM103446/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20190923 PL - United States TA - Infant Behav Dev JT - Infant behavior & development JID - 7806016 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - DNA Methylation/*physiology MH - Epigenesis, Genetic/physiology MH - Locomotion/*physiology MH - Male MH - Neuronal Plasticity/physiology MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord Injuries/*genetics/*metabolism/psychology PMC - PMC6878986 MID - NIHMS1543305 OTO - NOTNLM OT - DNA methylation OT - Development OT - Epigenetics OT - Locomotion OT - Plasticity OT - Spinal cord EDAT- 2019/09/27 06:00 MHDA- 2020/03/03 06:00 PMCR- 2020/11/01 CRDT- 2019/09/27 06:00 PHST- 2019/03/01 00:00 [received] PHST- 2019/08/15 00:00 [revised] PHST- 2019/09/11 00:00 [accepted] PHST- 2019/09/27 06:00 [pubmed] PHST- 2020/03/03 06:00 [medline] PHST- 2019/09/27 06:00 [entrez] PHST- 2020/11/01 00:00 [pmc-release] AID - S0163-6383(19)30060-8 [pii] AID - 10.1016/j.infbeh.2019.101381 [doi] PST - ppublish SO - Infant Behav Dev. 2019 Nov;57:101381. doi: 10.1016/j.infbeh.2019.101381. Epub 2019 Sep 23.