Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain

Marco, Eva M.; Echeverry‐Alzate, Víctor; López-Moreno, José Antonio; Giné, Elena; Peñasco, Sara; Viveros, María-Paz

doi:10.1097/fbp.0000000000000068

Cited by 75 publications

(51 citation statements)

References 52 publications

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“…These sex differences in the cannabinoid system may be important for key sex differences observed in behavior following stressors. Early-life stress affects the endocannabinoid system by (a) decreasing CB1Rs in adulthood in males 27 across various cortical regions as concluded through [ 3 H]CP55,940 binding and mRNA expression, though findings in females have been mixed 28 , and (b) increasing gene expression for endocannabinoid degradation enzymes 29 , though surprisingly these effects have not been studied in the cerebellum. Although endocannabinoids have not been thoroughly investigated in the cerebellum, males have been shown to exhibit increased cerebellar 2-AG compared to females 30 .…”

Section: Endocannabinoid Regulation Of Stressmentioning

confidence: 99%

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

Moussa-Tooks

Larson

Gimeno

et al. 2019

Preprint

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AbstractStudies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was 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 deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

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Section: Endocannabinoid Regulation Of Stressmentioning

confidence: 99%

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

Moussa-Tooks

Larson

Gimeno

et al. 2019

Preprint

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“…For example, MD results in sexually dimorphic decreases of cannabinoid receptor type 1 (CB 1 ) receptor expression and increases in CB 2 receptor expression and altered levels of enzymes involved in the biosynthesis and degradation of endocannabinoids in the hippocampus of P13 rodents (Suarez et al, ). In adolescence, several genes encoding components of the endocannabinoid system were increased in the frontal cortex of males and the hippocampus of females exposed to MD (Marco et al, ), and changes in the endocannabinoid system have been reported in the nucleus accumbens and frontal cortex of MS rats (Romano‐Lopez et al, ). Furthermore, early‐life stress is well known to induce depressive‐ and anxiety‐like behavioral phenotypes in adulthood (Daniels et al, ; Llorente et al, ; Marco et al, ), and recent studies from our laboratory have demonstrated an important role for anandamide activation of CB 1 receptors in the rostral ventromedial medulla in a rat model of hyperalgesia associated with depression/anxiety (Rea et al, ).…”

Section: Neurobiological Mechanisms Underlying the Association Betweementioning

confidence: 99%

Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms

Burke

Finn

McGuire

et al. 2016

J of Neuroscience Research

201

131

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A wealth of research over the past 2 decades has expanded our understanding of the impact of early-life adversity on physiological function and, consequently, health and wellbeing in later life. Early-life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early-life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic-pituitary-adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early-life psychological stress and chronic pain, is provided. Greater understanding of the impact of early-life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. © 2016 Wiley Periodicals, Inc.

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“…The error bars denote the SD of the relative activities. Comparisons were performed, and the P-values are labeled in the plot DAGLB has been linked to hypotrichosis and the influence of early life stress [44,45]. However, the evidence of DAGLB in lipid metabolism is limited.…”

Section: Discussionmentioning

confidence: 99%

A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study

et al. 2018

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Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (P = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.

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Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain

Cited by 75 publications

References 52 publications

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

Psychological stress in early life as a predisposing factor for the development of chronic pain: Clinical and preclinical evidence and neurobiological mechanisms

A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study

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