Frequent Low-Dose Δ9-Tetrahydrocannabinol in Adolescence Disrupts Microglia Homeostasis and Disables Responses to Microbial Infection and Social Stress in Young Adulthood

Lee, Hye-Lim; Jung, Kwang-Mook; Fotio, Yannick; Squire, Erica; Palese, Francesca; Lin, Lin; Torrens, Alexa; Ahmed, Faizy; Tagne, Alex Mabou; Ramirez, Jade; Su, Shiqi; Wong, Christina Renee; Jung, Daniel Hojin; Scarfone, Vanessa M.; Nguyen, Pauline U; Wood, Marcelo A.; Green, Kim Y.; Piomelli, Daniele

doi:10.1016/j.biopsych.2022.04.017

Cited by 25 publications

(21 citation statements)

References 82 publications

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“…We found that a daily low-intensity THC regimen (Torrens et al, 2020; Lee et al, 2022) dampened body weight gain in adolescent but not young adult mice. When adolescent THC treatment was stopped, the animals weighed less and expended more energy than did vehicle-treated controls.…”

Section: Discussionmentioning

confidence: 79%

“…Figures 1A and 1B illustrate the body weight trajectory of adolescent male and female mice (postnatal day, PND, 30-43) treated once daily with a dose of THC (5 mg/kg, intraperitoneal, IP) that, in mice of this age, produces only a modest decrease in body temperature (∼1°C) and no change in motor activity or food intake (Torrens et al, 2020; Lee et al, 2022). THC-exposed mice of both sexes gained significantly less weight than did control animals treated only with vehicle.…”

Section: Resultsmentioning

confidence: 99%

“…THC was dissolved in a vehicle of Tween 80/sterile saline (5:95, v/v) and was administered once daily on PND30-43, unless specified otherwise. The pharmacokinetic and pharmacodynamic properties of the THC dose selected for the present study (5 mg/kg) are described in detail elsewhere (Torrens et al, 2020; Lee et al, 2022). AM251, AM6545 and AM630 were dissolved in dimethyl sulfoxide (DMSO) in sterile saline (5:95, v/v) and administered by IP injection 60 min before THC.…”

Section: Experimental Model and Subject Detailsmentioning

confidence: 99%

“…RNA isolation: Total RNA was extracted as described (Lee et al, 2022). Samples with RNA integrity number ≥ 8.5 were used for RNA sequencing.…”

Section: Transcriptomic Analysesmentioning

confidence: 99%

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Adolescent Exposure to Low-Dose THC Disrupts Energy Balance and Adipose Organ Homeostasis in Adulthood

Lin

Jung

et al. 2022

Preprint

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One of cannabis′ most iconic effects is the stimulation of hedonic high-calorie eating - the ′munchies′ - yet habitual cannabis users are on average leaner than non-users. We asked whether this unexpected phenotype might result from lasting changes in energy balance established during adolescence, when habitual use of the drug often begins. We found that daily low-dose administration of cannabis′ intoxicating constituent, delta-9-tetrahydrocannabinol (THC), to adolescent mice causes an adult metabolic phenotype characterized by reduced fat mass, increased lean mass and utilization of fat as fuel, partial resistance to diet-induced obesity and dyslipidemia, and enhanced thermogenesis. Multi-omics analyses revealed that this phenotype is associated with multiple molecular anomalies in the adipose organ, which include ectopic overexpression of muscle-associated proteins and heightened anabolic processing. Thus, adolescent exposure to THC may promote an enduring ′pseudo-lean′ state that superficially resembles healthy leanness but might in fact be rooted in adipose organ dysfunction.

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Section: Discussionmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Section: Experimental Model and Subject Detailsmentioning

confidence: 99%

“…RNA isolation: Total RNA was extracted as described (Lee et al, 2022). Samples with RNA integrity number ≥ 8.5 were used for RNA sequencing.…”

Section: Transcriptomic Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Adolescent Exposure to Low-Dose THC Disrupts Energy Balance and Adipose Organ Homeostasis in Adulthood

Lin

Jung

et al. 2022

Preprint

Self Cite

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“…Moreover, phytocannabinoids can easily cross the BBB and directly target the fetal ECS, potentially affecting neurotransmission, synaptogenesis, and microglia activity in the offspring’s developing brain [ 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 ]. These neurochemical alterations might contribute to the higher susceptibility to develop neurodevelopmental and psychiatric disorders in the children of mothers who used Cannabis during pregnancy [ 28 , 29 , 222 , 224 ].…”

Section: From Parent To Offspring: When Cannabis T...mentioning

confidence: 99%

Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy

Rava

Trezza

2023

IJMS

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In recent years, Cannabis use/misuse for treating pregnancy-related symptoms and other chronic conditions has increased among pregnant women, favored by decriminalization and/or legalization of its recreational uses in addition to its easy accessibility. However, there is evidence that prenatal Cannabis exposure might have adverse consequences on pregnancy progression and a deleterious impact on proper neurodevelopmental trajectories in the offspring. Maternal Cannabis use could interfere with the complex and finely controlled role performed by the endocannabinoid system in reproductive physiology, impairing multiple gestational processes from blastocyst implantation to parturition, with long-lasting intergenerational effects. In this review, we discuss current clinical and preclinical evidence regarding the role of endocannabinoids in development, function, and immunity of the maternal–fetal interface, focusing on the impact of Cannabis constituents on each of these gestational processes. We also discuss the intrinsic limitations of the available studies and the future perspectives in this challenging research field.

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Lipopolysaccharide-induced endotoxaemia during adolescence promotes stress vulnerability in adult mice via deregulation of nuclear factor erythroid 2-related factor 2 in the medial prefrontal cortex

et al. 2023

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Frequent Low-Dose Δ9-Tetrahydrocannabinol in Adolescence Disrupts Microglia Homeostasis and Disables Responses to Microbial Infection and Social Stress in Young Adulthood

Cited by 25 publications

References 82 publications

Adolescent Exposure to Low-Dose THC Disrupts Energy Balance and Adipose Organ Homeostasis in Adulthood

Adolescent Exposure to Low-Dose THC Disrupts Energy Balance and Adipose Organ Homeostasis in Adulthood

Emerging Roles of Endocannabinoids as Key Lipid Mediators for a Successful Pregnancy

Lipopolysaccharide-induced endotoxaemia during adolescence promotes stress vulnerability in adult mice via deregulation of nuclear factor erythroid 2-related factor 2 in the medial prefrontal cortex

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