Endocannabinoid release at ventral hippocampal-amygdala synapses regulates stress-induced behavioral adaptation

Kondev, Veronika; Najeed, Mustafa; Yasmin, Farhana; Morgan, Amanda; Loomba, Niharika; Johnson, Keenan; Adank, Danielle N.; Dong, Ao; Delpire, Eric; Li, Yulong; Winder, Danny; Grueter, Brad A.; Patel, Sachin

doi:10.1016/j.celrep.2023.113027

Cited by 9 publications

(1 citation statement)

References 54 publications

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“…Hence, albeit processing was about equal for all subjects of the present cohort and results are comparable within this study, the endocannabinoid concentrations in nanogram per milliliter obtained herein are likely too high as compared with healthy plasma levels obtained in samples, which were immediately centrifuged and frozen [51,73]. The processing time is less critical for sphingolipids and untargeted lipidomic analyses of abundant lipids, which were the focus in the present study, but this is still a limitation because endocannabinoids are considered as master regulators of stress, stress relief, reward and coping strategies that are used to fend off stressevoked health risks such as hypertension [60,[74][75][76]. In this regard, we observed that palmitoylethanolamide (PEA) was increased in women and in men with a medical history of hypertension.…”

Section: Discussionmentioning

confidence: 92%

Sex, age, body mass index, and contraceptive use but not perceived stress influence healthy plasma lipidomic profiles

Hahnefeld,

Hackel,

Trautmann

et al. 2024

Preprint

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Background The stress of everyday life is thought to contribute to the pathogenesis of metabolic, vascular, mental, and immune diseases, with different susceptibilities in women and men. We hypothesized that sex differences in stress perception may manifest in sex-dependent lipid profiles. Methods The present study investigated the effect of sex, age, body mass index, perceived stress, regular and occasional drug use, and dietary supplements on plasma lipidomic profiles, obtained by mass spectrometry analyses. The study included 217 healthy women and 108 healthy men aged 18–68 years, who were recruited in a 2:1 female:male ratio to account for women with/without contraceptives. Results As expected, dehydroepiandrosterone sulfate (DHEAS) and ceramides were higher in men than in women, and in both sexes DHEAS decreased with age, while ceramides increased. Contrary to expectations, neither DHEAS nor ceramides were associated with perceived stress (PSQ30 questionnaire), which peaked in young and 51 + women (low in ages between), and in obese young men, whereas the overall male PSQ30 peak was around 40 years of age. None of the lipid species or classes showed a similar "age X sex X BMI" interaction. Strong sex differences were found for lysophosphatidylcholines (LPCs) (low in women) and their metabolites, lysophosphatidic acids (LPAs) (high in women). The LPA:LPC ratio was particularly high in women receiving contraceptives suggesting a strong hormone-induced conversion of LPCs to LPAs via autotaxin, which was much higher in women than in men, and is known to trigger platelet aggregation. In addition, phosphatidylethanolamines (PE) were high in women. They are precursors of endocannabinoids such as palmitoylethanolamide (PEA), which was elevated in subjects with a medical history of hypertension and increased with the BMI. Conclusion The results reveal complex sex differences in perceived stress and lipidomic profiles, the latter being exacerbated by contraceptive use, but perceived stress and lipids were not directly correlated. Trial registration Not applicable

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