Δ9-Tetrahydrocannabinol changes the brain lipidome and transcriptome differentially in the adolescent and the adult.
Emma Leishman, Michelle Murphy, Ken Mackie, Heather B. Bradshaw
Biochimica et biophysica acta. Molecular and cell biology of lipids May 2018 DOI: 10.1016/j.bbalip.2018.02.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Female mice (adolescent and adult) |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Duration | Acute (single dose) |
| Topics | Cannabis |
| Keywords | Adolescent brain Endocannabinoid Lipidomics Lipoamine Transcriptomic |
| Key points | A single dose of THC caused age-dependent lipidomic and transcriptomic changes in the female mouse brain, with adults showing more changes than adolescents; endocannabinoids and related lipids mostly decreased in adults, and 31 genes were regulated in the hippocampus at both ages, suggesting a conserved response to THC exposure. |
Abstract
Exposing the adolescent brain to drugs of abuse is associated with increased risk for adult onset psychopathologies. Cannabis use peaks during adolescence, with largely unknown effects on the developing brain. Cannabis' major psychoactive component, Δ9-tetrahydrocannabinol (THC) alters neuronal, astrocytic, and microglial signaling. Therefore, multiple cellular and signaling pathways are affected with a single dose of THC. The endogenous cannabinoids (eCBs), N-arachidonoyl ethanolamine (AEA) and 2-arachidonoyl glycerol (2-AG) are members of an interconnected lipidome that includes an emerging class of AEA structural analogs, the lipoamines, additional 2-acyl glycerols, free fatty acids, and prostaglandins (PGs). Lipids in this lipidome share many biosynthetic and metabolic pathways, yet have diverse signaling properties. Here, we show that acute THC drives age-dependent changes in this lipidome across 8 regions of the female mouse brain. Interestingly, most changes are observed in the adult, with eCBs and related lipids predominately decreasing. Analysis of THC and metabolites reveals an unequal distribution across these brain areas; however, the highest levels of THC were measured in the hippocampus (HIPP) in all age groups. Transcriptomic analysis of the HIPP after acute THC showed that like the lipidome, the adult transcriptome demonstrated significantly more changes than the adolescent. Importantly, the regulation of 31 genes overlapped between the adolescent and the adult, suggesting a conserved transcriptomic response in the HIPP to THC exposure independent of age. Taken together these data illustrate that the first exposure to a single dose of THC has profound effects on signaling in the CNS.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
Cites 12
- Sex‐dependent long‐term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats British Journal of Pharmacology November 15, 2013
- Disruption of hippocampal synaptic transmission and long‐term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9‐tetrahydrocannabinol Addiction Biology January 5, 2016
- Cortical neuroinflammation contributes to long-term cognitive dysfunctions following adolescent delta-9-tetrahydrocannabinol treatment in female rats. European Neuropsychopharmacology December 2015
- Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex. Neurobiology of Disease 2015
- Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling. Cell November 21, 2013
and 7 more in the library