Abstract

Emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling with studies on stress-induced endocannabinoid dysregulation focusing on cerebral changes that are temporally proximal to stressors. Little is known about temporally distal and sex-specific effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Following limited bedding at postnatal days 2–9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids, related lipids, and mRNA were assessed, and behavioral performance evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar interpositus nucleus in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Cerebellar interpositus transcriptomics revealed substantial sex effects, with minimal stress effects. Stress did impair novel object recognition in both sexes and social preference in females. Accordingly, the cerebellar endocannabinoid system exhibits robust sex-specific differences, malleable through early-life stress, suggesting the role of endocannabinoids and stress to sexual differentiation of the brain and cerebellar-related dysfunctions.

Details

Title
Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress
Author
Moussa-Tooks, Alexandra B 1 ; Larson, Eric R 2 ; Gimeno, Alex F 2 ; Leishman, Emma 1 ; Bartolomeo, Lisa A 2 ; Bradshaw, Heather B 1 ; Green, John T 3 ; O’Donnell Brian F 4 ; Mackie, Ken 5 ; Hetrick, William P 4 

 Indiana University, Psychological and Brain Sciences, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X); Indiana University, Program in Neuroscience, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
 Indiana University, Psychological and Brain Sciences, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
 University of Vermont, Department of Psychological Science, Burlington, USA (GRID:grid.59062.38) (ISNI:0000 0004 1936 7689) 
 Indiana University, Psychological and Brain Sciences, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X); Indiana University, Program in Neuroscience, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X); Indiana University School of Medicine, Department of Psychiatry, Indianapolis, USA (GRID:grid.257413.6) (ISNI:0000 0001 2287 3919) 
 Indiana University, Psychological and Brain Sciences, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X); Indiana University, Program in Neuroscience, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X); Indiana University, Linda and Jack Gill Center for Biomolecular Science, Bloomington, USA (GRID:grid.411377.7) (ISNI:0000 0001 0790 959X) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2396292765
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.