Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Navarro, Daniela; Gasparyan, Ani; Navarrete, Francisco; Torregrosa, Abraham B; Rubio, Gabriel; Marín-Mayor, Marta; Acosta, Gabriela Beatriz; García-Gutiérrez, María Salud; Manzanares, Jorge

doi:10.3390/ijms23094764

Cited by 17 publications

(14 citation statements)

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“…As such, a defined involvement for miR 200a and miR 200b in depression-like behaviour remains to be explored. However, several of the target genes, some of which by themselves act as regulators of gene expression (such as the transcription factors jun and atf3 ) have been demonstrated to be relevant to psychiatric disorders (including nr3c1 , the glucocorticoid receptor [ 70 , 71 ]; ntrk2, the receptor for brain-derived neurotrophic factor; [ 72 , 73 ] and cnr1 , the cannabinoid receptor 1 [ 74 , 75 ]). Hence, miR 200a and miR 200b and their target genes may constitute a gene regulatory network that forms the molecular basis for the pathophysiological events underlying the consequences early-life ID on affective behaviour.…”

Section: Discussionmentioning

confidence: 99%

Early-life iron deficiency persistently disrupts affective behaviour in mice

et al. 2023

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Background/Objective Iron deficiency (ID) is the most common nutrient deficiency, affecting two billion people worldwide, including about 30% of pregnant women. During gestation, the brain is particularly vulnerable to environmental insults, which can irrevocably impair critical developmental processes. Consequently, detrimental consequences of early-life ID for offspring brain structure and function have been described. Although early life ID has been associated with an increased long-term risk for several neuropsychiatric disorders, the effect on depressive disorders has remained unresolved. Materials and methods A mouse model of moderate foetal and neonatal ID was established by keeping pregnant dams on an iron-deficient diet throughout gestation until postnatal day 10. The ensuing significant decrease of iron content in the offspring brain, as well as the impact on maternal behaviour and offspring vocalization was determined in the first postnatal week. The consequences of early-life ID for depression- and anxiety-like behaviour in adulthood were revealed employing dedicated behavioural assays. miRNA sequencing of hippocampal tissue of offspring revealed specific miRNAs signatures accompanying the behavioural deficits of foetal and neonatal ID in the adult brain. Results Mothers receiving iron-deficient food during pregnancy and lactation exhibited significantly less licking and grooming behaviour, while active pup retrieval and pup ultrasonic vocalizations were unaltered. Adult offspring with a history of foetal and neonatal ID showed an increase in depression- and anxiety-like behaviour, paralleled by a deranged miRNA expression profile in the hippocampus, specifically levels of miR200a and miR200b. Conclusion ID during the foetal and neonatal periods has life-long consequences for affective behaviour in mice and leaves a specific and persistent mark on the expression of miRNAs in the brain. Foetal and neonatal ID needs to be further considered as risk factor for the development of depression and anxiety disorders later in life. Key Messages Marginal reduction of gestational alimentary iron intake decreases brain iron content of the juvenile offspring. Early-life ID is associated with increased depression- and anxiety-like behaviour in adulthood. Reduction of maternal alimentary iron intake during pregnancy is reflected in an alteration of miRNA signatures in the adult offspring brain.

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Section: Discussionmentioning

confidence: 99%

Early-life iron deficiency persistently disrupts affective behaviour in mice

et al. 2023

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“…Evidence is increasing regarding the role of eCB in mood regulation. Clinical studies have shown altered endocannabinoid signaling in psychiatric patients [ 182 ]. Genetic polymorphisms in CB1R and CB2R are associated with major depression, bipolar disorder, and resistance to therapy, which has been observed in depressed patients who have a single-nucleotide polymorphism in CB1R [ 183 , 184 , 185 , 186 ].…”

Section: Endocannabinoid System Emerging As a Pharmacotherapy Target ...mentioning

confidence: 99%

Endocannabinoid System: Chemical Characteristics and Biological Activity

Rezende

Alencar²,

de³

et al. 2023

Pharmaceuticals

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The endocannabinoid system (eCB) has been studied to identify the molecular structures present in Cannabis sativa. eCB consists of cannabinoid receptors, endogenous ligands, and the associated enzymatic apparatus responsible for maintaining energy homeostasis and cognitive processes. Several physiological effects of cannabinoids are exerted through interactions with various receptors, such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered G-protein-coupled receptors (GPR55, GPR3, GPR6, GPR12, and GPR19). Anandamide (AEA) and 2-arachidoylglycerol (2-AG), two small lipids derived from arachidonic acid, showed high-affinity binding to both CB1 and CB2 receptors. eCB plays a critical role in chronic pain and mood disorders and has been extensively studied because of its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities for eCB and are relevant to the treatment of several neurological diseases. This review provides a description of eCB components and discusses how phytocannabinoids and other exogenous compounds may regulate the eCB balance. Furthermore, we show the hypo- or hyperfunctionality of eCB in the body and how eCB is related to chronic pain and mood disorders, even with integrative and complementary health practices (ICHP) harmonizing the eCB.

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“…The endogenous cannabinoid or endocannabinoid system has been identified as playing a significant role in several psychiatric disorders, as well as in suicidal behaviour [142,143]. These effects appear to be mediated primarily through the cannabinoid type 1 (CB1) receptor, which is expressed at high levels in several key brain regions, including the prefrontal cortex and limbic system [144]. In a rat model, changes in social behaviour and sensitivity to physical or social pain caused by rejection were associated with an upregulation of CB1 receptors.…”

Section: E4 Cannabinoid Receptor Agonistsmentioning

confidence: 99%

Pharmacotherapy for the Secondary Prevention of Suicide: Leads from the Social Pain Hypothesis

Rajkumar¹

2022

Preprint

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Suicidal behaviour is a public health problem whose magnitude is both substantial and increasing. Since many individuals seek medical treatment following a suicide attempt, strategies aimed at reducing further attempts in this population are a valid and feasible secondary prevention approach. An evaluation of the available evidence suggests that existing treatment approaches have limited efficacy in this setting, highlighting the need for innovative approaches to suicide prevention. Existing research on the neurobiology of social pain has highlighted the importance of this phenomenon as a risk factor for suicide, and has also yielded several attractive targets for pharmacological preventive strategies. In this paper, the available evidence related to these targets is synthesized and critically evaluated. The way in which social pain is related to the “anti-suicidal” properties of recently approved treatments, such as ketamine and psilocybin, is also examined. Such strategies may be effective for the short-term reduction of suicidal ideation and behaviour in individuals who have made a suicide attempt suicide prevention, particularly in cases where social pain is identified as a contributory factor. These pharmacological approaches may be effective regardless of the presence or absence of a specific psychiatric diagnosis.

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Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders

Cited by 17 publications

References 473 publications

Early-life iron deficiency persistently disrupts affective behaviour in mice

Early-life iron deficiency persistently disrupts affective behaviour in mice

Endocannabinoid System: Chemical Characteristics and Biological Activity

Pharmacotherapy for the Secondary Prevention of Suicide: Leads from the Social Pain Hypothesis

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