Sterol Carrier Protein‐2/Sterol Carrier Protein‐x/Fatty Acid Binding Protein‐1 Ablation Impacts Response of Brain Endocannabinoid to High‐Fat Diet

Martin, Gregory G.; Seeger, Drew R.; McIntosh, Avery L.; Milligan, Sherrelle; Chung, Sarah; Landrock, Danilo; Dangott, Lawrence J.; Golovko, Mikhail Y.; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

doi:10.1002/lipd.12192

Cited by 9 publications

(9 citation statements)

References 73 publications

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“…The influence of sterol carrier protein-2 upon anandamide metabolism in vivo is not known; however, deletion of sterol carrier protein-2 in concert with the liver-specific FABP1 isoform did not alter brain anandamide levels (Martin et al, 2019).…”

Section: Intracellular Endocannabinoid Transportmentioning

confidence: 94%

“…Overexpression of sterol carrier protein‐2 increased the cellular uptake of anandamide, demonstrating a functional role for sterol carrier protein‐2 in anandamide accumulation (Liedhegner et al, 2014). The influence of sterol carrier protein‐2 upon anandamide metabolism in vivo is not known; however, deletion of sterol carrier protein‐2 in concert with the liver‐specific FABP1 isoform did not alter brain anandamide levels (Martin et al, 2019).…”

Section: Intracellular Endocannabinoid Transportmentioning

confidence: 99%

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Mechanisms of endocannabinoid transport in the brain

Kaczocha

Haj‐Dahmane

2021

British J Pharmacology

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The endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide are among the best studied lipid messengers in the brain. By activating cannabinoid receptors in the CNS, endocannabinoids tune synaptic function, thereby influencing a variety of physiological and behavioural processes. Extensive research conducted over the last few decades has considerably enhanced our understanding of the molecular mechanisms and physiological functions of the endocannabinoid system. It is now well-established that endocannabinoids are synthesized by postsynaptic neurons and serve as retrograde messengers that suppress neurotransmitter release at central synapses. While the detailed mechanisms by which endocannabinoids gate synaptic function and behavioural processes are relatively well characterized, the mechanisms governing endocannabinoid transport at central synapses remain ill defined. Recently, several studies have begun to unravel the mechanisms governing intracellular and intercellular endocannabinoid transport. In this review, we will focus on new advances in the mechanisms of intracellular and synaptic endocannabinoid transport in the CNS.

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Section: Intracellular Endocannabinoid Transportmentioning

confidence: 94%

Section: Intracellular Endocannabinoid Transportmentioning

confidence: 99%

Mechanisms of endocannabinoid transport in the brain

Kaczocha

Haj‐Dahmane

2021

British J Pharmacology

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“…SCP‐2 is present in brain and is enriched in synaptosomal preparations (Myers‐Payne et al, 1996), observations that support its potential for regulating the ECS system at the synapse. Studies using SCP‐2 knock out mice fed a high‐fat diet suggest that SCP‐2 plays a role in regulating eCB concentrations in the brain; however, the effect may be secondary to changes in arachidonic acid concentrations in the circulation (Martin et al, 2019).…”

Section: Selected Recent Discoveries Regarding Components Of the Ecs ...mentioning

confidence: 99%

Endocannabinoid signaling in the central nervous system

Ramirez

Ruiz‐Pérez

Stollenwerk

et al. 2022

Glia

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It is hard to overestimate the influence of the endocannabinoid signaling (ECS) system on central nervous system (CNS) function. In the 40 years since cannabinoids were found to trigger specific cell signaling cascades, studies of the ECS system continue to cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in the CNS and regulate cell-cell communication via effects on the release of both neurotransmitters and gliotransmitters. CB2 cannabinoid receptors are difficult to detect in the CNS but seem to "punch above their weight" as compounds targeting these receptors have significant effects on inflammatory state and behavior. Positive and negative allosteric modulators for both receptors have been identified and examined in preclinical studies. Concentrations of the endocannabinoid ligands, N-arachidonoylethanolamine and 2-arachidonoylglycerol (2-AG), are regulated by a combination of enzymatic synthesis and degradation and inhibitors of these processes are available and making their way into clinical trials. Importantly, ECS regulates many essential brain functions, including regulation of reward, anxiety, inflammation, motor control, and cellular development. While the field is on the cusp of preclinical discoveries providing impactful clinical and therapeutic insights into many CNS disorders, there is still much to be learned about this remarkable and versatile modulatory system.

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“…The SCP2 protein has been proposed to regulate brain endocannabinoid levels and, thus, endocannabinoid system function (Liedhegner et al, 2014;Martin et al, 2019). The Scp2 gene contains a putative splice region variant and demonstrates genetic modulation of expression (cis eQTL) in naive BXD neocortex and prefrontal cortex.…”

Section: Sterol Carrier Protein 2 (Scp2) Is a Positional Candidate For Modulation Of The Analgesic Response To Thcmentioning

confidence: 99%

Genetic Modulation of Initial Sensitivity to Δ9-Tetrahydrocannabinol (THC) Among the BXD Family of Mice

et al. 2021

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Cannabinoid receptor 1 activation by the major psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), produces motor impairments, hypothermia, and analgesia upon acute exposure. In previous work, we demonstrated significant sex and strain differences in acute responses to THC following administration of a single dose (10 mg/kg, i.p.) in C57BL/6J (B6) and DBA/2J (D2) inbred mice. To determine the extent to which these differences are heritable, we quantified acute responses to a single dose of THC (10 mg/kg, i.p.) in males and females from 20 members of the BXD family of inbred strains derived by crossing and inbreeding B6 and D2 mice. Acute THC responses (initial sensitivity) were quantified as changes from baseline for: 1. spontaneous activity in the open field (mobility), 2. body temperature (hypothermia), and 3. tail withdrawal latency to a thermal stimulus (antinociception). Initial sensitivity to the immobilizing, hypothermic, and antinociceptive effects of THC varied substantially across the BXD family. Heritability was highest for mobility and hypothermia traits, indicating that segregating genetic variants modulate initial sensitivity to THC. We identified genomic loci and candidate genes, including Ndufs2, Scp2, Rps6kb1 or P70S6K, Pde4d, and Pten, that may control variation in THC initial sensitivity. We also detected strong correlations between initial responses to THC and legacy phenotypes related to intake or response to other drugs of abuse (cocaine, ethanol, and morphine). Our study demonstrates the feasibility of mapping genes and variants modulating THC responses in the BXDs to systematically define biological processes and liabilities associated with drug use and abuse.

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Sterol Carrier Protein‐2/Sterol Carrier Protein‐x/Fatty Acid Binding Protein‐1 Ablation Impacts Response of Brain Endocannabinoid to High‐Fat Diet

Cited by 9 publications

References 73 publications

Mechanisms of endocannabinoid transport in the brain

Mechanisms of endocannabinoid transport in the brain

Endocannabinoid signaling in the central nervous system

Genetic Modulation of Initial Sensitivity to Δ9-Tetrahydrocannabinol (THC) Among the BXD Family of Mice

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