Mechanisms of endocannabinoid control of synaptic plasticity

Winters, Bryony L.; Vaughan, Christopher W.

doi:10.1016/j.neuropharm.2021.108736

Cited by 35 publications

(26 citation statements)

References 407 publications

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“…In contrast, operation of the immunocompetent system was first identified as a site of CB2 expression, followed by its discovery in peripheral nerves ( 22 ); CB2 is now recognized as part of the central nervous system (CNS) physiology ( 23 ). Importantly, the binding of eCB to the cannabinoid receptors was reported to facilitate the neuroplasticity of synaptic processes ( 5 , 24 , 25 ).…”

Section: Current Status Of Knowledgementioning

confidence: 99%

“…Therefore, dietary lipids can be a fundamental factor that determines the types and amounts of eCBs and OxLs biosynthesized, and consequently, the effects of these bioactive lipids on cellular events, including those in the nervous system. The evidence for exercise elaboration of eCBs in the brain is revealing a better understanding of the benefits of exercise ( 3 ), from the young to the adult, especially as the interaction of physical activity and well-being are examined ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…The endogenous production of AEA and 2-AG, and of N- docosahexaenoyl ethanolamide (DHEA) and N- eicosapentaenoyl ethanolamide (EPEA)—both products of DHA and EPA—is dependent upon tissue concentrations of n–6 and n–3 PUFAs, respectively. The amounts of n–3 PUFAs can shift the formation of n–3-derived eCBs ( 5 ) from AEA and 2-AG, and highlights the importance of understanding the effects of DHEA and EPEA. Furthermore, the biosynthesis of the OxLs via cyclooxygenase enzymes (COX1 and COX2) and lipoxygenase enzymes (LOX) uses similar families of PUFA substrates ( Figure 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…The first objective is to present evidence for the relations between PUFAs, eCBs, and OxLs in brain physiology and neuroinflammation. The second objective is to describe the impact of exercise, which supports brain plasticity ( 10 ), with eCBs facilitating synaptic plasticity ( 5 ), and its consequences for pain and well-being.…”

Section: Introductionmentioning

confidence: 99%

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Dietary PUFAs and Exercise Dynamic Actions on Endocannabinoids in Brain: Consequences for Neural Plasticity and Neuroinflammation

Park

Watkins

2022

Advances in Nutrition

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The brain and peripheral nervous system provide oversight to muscle physiology and metabolism. Muscle is the largest organ in the body and critical for glucose sensitivity, prevention of diabetes, and control of obesity. The central nervous system produces endocannabinoids (eCBs) that play a role in brain neurobiology, such as inflammation and pain. Interestingly, studies in humans and rodents show that a moderate duration of exercise increases eCBs in the brain and blood and influences cannabinoid receptors. Cannabinoid actions in the nervous system have advanced our understanding of pain, well-being, and disease. Nutrition is an important aspect of brain and eCB physiology because eCBs are biosynthesized from PUFAs. The primary eCB metabolites are derived from arachidonic acid, a 20:4n–6 (ω-6) PUFA, and the n–3 (ω-3) PUFAs, EPA and DHA. The eCBs bind to cannabinoid receptors CB1 and CB2 to exert a wide range of activities, such as stimulating appetite, influencing energy metabolism, supporting the immune system, and facilitating neuroplasticity. A diet containing different essential n–6 and n–3 PUFAs will dominate the formation of specific eCBs, and subsequently their actions as ligands for CB1 and CB2. The eCBs also function as substrates for cyclooxygenase enzymes, including potential substrates for the oxylipins (OxLs), which can be proinflammatory. Together, the eCBs and OxLs act as modulators of neuroinflammation. Thus, dietary PUFAs have implications for exercise responses via synthesis of eCBs and their effects on neuroinflammation. Neurotrophins also participate in interactions between diet and the eCBs, specifically brain-derived neurotrophic factor (BDNF). BDNF supports neuroplasticity in cooperation with the endocannabinoid system (ECS). This review will describe the role of PUFAs in eCB biosynthesis, discuss the ECS and OxLs in neuroinflammation, highlight the evidence for exercise effects on eCBs, and describe eCB and BDNF actions on neuroplasticity.

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Section: Current Status Of Knowledgementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dietary PUFAs and Exercise Dynamic Actions on Endocannabinoids in Brain: Consequences for Neural Plasticity and Neuroinflammation

Park

Watkins

2022

Advances in Nutrition

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“…DHEA and EPEA have been reported to exhibit various immunomodulatory and anti-inflammatory activities and effects on food intake and mood ( 20 , 178 ). The eCBs can induce short-term changes and long-term synaptic plasticity in the whole nervous system, because eCBs synthesized in the postsynaptic neurons can function reversely to regulate the presynaptic input ( 179 ). Maternal omega-3 PUFAs deficiency can induce the impairment of eCBs gating of LTP in hippocampus of weaned pups ( 180 ).…”

Section: Possible Anti-depressant Mechanisms Of Action Of Omega-3 Pufasmentioning

confidence: 99%

Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system

et al. 2022

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Omega-3 polyunsaturated fatty acids (PUFAs) can play important roles in maintaining mental health and resistance to stress, and omega-3 PUFAs supplementation can display beneficial effects on both the prevention and treatment of depressive disorders. Although the underlying mechanisms are still unclear, accumulated evidence indicates that omega-3 PUFAs can exhibit pleiotropic effects on the neural structure and function. Thus, they play fundamental roles in brain activities involved in the mood regulation. Since depressive symptoms have been assumed to be of central origin, this review aims to summarize the recently published studies to identify the potential neurobiological mechanisms underlying the anti-depressant effects of omega-3 PUFAs. These include that of (1) anti-neuroinflammatory; (2) hypothalamus-pituitary-adrenal (HPA) axis; (3) anti-oxidative stress; (4) anti-neurodegeneration; (5) neuroplasticity and synaptic plasticity; and (6) modulation of neurotransmitter systems. Despite many lines of evidence have hinted that these mechanisms may co-exist and work in concert to produce anti-depressive effects, the potentially multiple sites of action of omega-3 PUFAs need to be fully established. We also discussed the limitations of current studies and suggest future directions for preclinical and translational research in this field.

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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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Mechanisms of endocannabinoid control of synaptic plasticity

Cited by 35 publications

References 407 publications

Dietary PUFAs and Exercise Dynamic Actions on Endocannabinoids in Brain: Consequences for Neural Plasticity and Neuroinflammation

Dietary PUFAs and Exercise Dynamic Actions on Endocannabinoids in Brain: Consequences for Neural Plasticity and Neuroinflammation

Possible antidepressant mechanisms of omega-3 polyunsaturated fatty acids acting on the central nervous system

Endocannabinoid signaling in the central nervous system

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