Neuroinflammation and depression: A review

European Journal of Neuroscience, Journal Year: 2020, Volume and Issue: 53(1), P. 151 - 171

Published: March 9, 2020

Abstract Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor interacts with the three neurobiological correlates of major depressive disorder: depletion brain serotonin, dysregulation hypothalamus–pituitary–adrenal (HPA) axis alteration continuous production adult‐generated neurons in dentate gyrus hippocampus. This review discusses main players immunity as well how inflammation above mechanisms. It reported kynurenine (KYN) pathway favour its excitotoxic component HPA have common effect increasing extracellular glutamate levels neurotransmission, which can impact hippocampal neurogenesis. pathophysiological cascade appears to be triggered or sustained reinforced by any chronic inflammatory condition involving increased circulating markers are able cross blood–brain barrier activate microglia; it also consequence primary neuroinflammation, such neurodegenerative disorders early manifestations frequently symptoms. Further data indicate microglial activation may result from direct stress on vascular function. The intricated dynamic crosstalk between other relevant depression add therapeutic target for future strategies disorder.

Language: Английский

---

Tryptophan Metabolism in Depression: A Narrative Review with a Focus on Serotonin and Kynurenine Pathways

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8493 - 8493

Published: July 31, 2022

Depression is a common and serious disorder, characterized by symptoms like anhedonia, lack of energy, sad mood, low appetite, sleep disturbances. This disease very complex not totally elucidated, in which diverse molecular biological mechanisms are involved, such as neuroinflammation. There high need for the development new therapies gaining insights into this urgent. One important player depression amino acid tryptophan. can be metabolized two pathways context depression: serotonin kynurenine pathways. These metabolic tryptophan crucial several processes that linked with depression. Indeed, maintenance balance critical human physiological homeostasis. Thus, narrative review aims to explore metabolism (particularly pathways) depression, starting global overview about these topics ending focus on neuroinflammation, stress, microbiota, brain-derived neurotrophic factor regulation disease. Taken together, information clarify particularly

Language: Английский

---

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 734 - 734

Published: June 25, 2021

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% catabolized. activated by acute and chronic immune responses leading to wide range illnesses including cancer, diseases, neurodegenerative diseases psychiatric disorders. presence positive feedback loops facilitates amplifying the vice versa. TRP-KYN synthesizes multifarious metabolites oxidants, antioxidants, neurotoxins, neuroprotectants immunomodulators. immunomodulators are known facilitate system towards tolerogenic state, resulting in low-grade inflammation (LGI) that commonly present obesity, poor nutrition, exposer chemicals or allergens, prodromal stage various diseases. KYN, kynurenic acid, xanthurenic acid cinnabarinic aryl hydrocarbon receptor ligands serve as Furthermore, enzymes be stress hormone cortisol inflammatory cytokines, genotypic variants were observed contribute thus 2,3-dioxygenase, indoleamine 2,3-dioxygenases kynurenine-3-monooxygenase pathway. This review article discusses with special emphasis on its interaction shift LGI overviews major symptoms, pro- anti-inflammatory cytokines toxic protective KYNs explore linkage between LGI, KYNs, disorders, depressive disorder, bipolar substance use post-traumatic schizophrenia autism spectrum disorder.

Language: Английский

---

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Pharmacological Reviews, Journal Year: 2020, Volume and Issue: 73(1), P. 202 - 277

Published: Dec. 16, 2020

Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food Drug Administration a new class antidepressants, 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin lysergic acid diethylamide (LSD) are being investigated several II I trials. Hence, concept psychedelics may be incorporated into modern society. Here, we discuss main known neurobiological therapeutic mechanisms psychedelics, which thought to mediated effects these on serotonergic (via 5-HT_2A 5-HT_1A receptors) glutamatergic [via N-methyl-d-aspartate (NMDA) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors] systems. We focus 1) neuroplasticity modulation mammalian target rapamycin–, brain-derived neurotrophic factor–, early growth response–related pathways; 2) immunomodulation via hypothalamic-pituitary-adrenal axis, nuclear factor ĸB, cytokines such tumor necrosis factor-α interleukin 1, 6, 10 production release; 3) serotonergic, dopaminergic, glutamatergic, GABAergic, norepinephrinergic receptors, transporters, turnover arising concerns ways assess changes, dependence, immunosuppression. Although larger cohorts required corroborate preliminary findings, results obtained so far promising represent critical opportunity improvement pharmacotherapies psychiatry, an area that seen limited advancement last 20 years. Studies underway trying decouple from compounds.

Significance Statement

Psychedelic emerging However, understanding molecular mediating remains limited. This paper reviews available concerning pathways modulate neuroplasticity, immunity, neurotransmitter work aims reference psychiatrists who soon faced with possibility prescribing medications, helping them compound(s) regimen could most useful decreasing specific psychiatric symptoms.

Language: Английский

---

Biological Properties of Vitamins of the B-Complex, Part 1: Vitamins B1, B2, B3, and B5

Nutrients, Journal Year: 2022, Volume and Issue: 14(3), P. 484 - 484

Published: Jan. 22, 2022

This review summarizes the current knowledge on essential vitamins B

Language: Английский

---

Associations among peripheral and central kynurenine pathway metabolites and inflammation in depression

Neuropsychopharmacology, Journal Year: 2020, Volume and Issue: 45(6), P. 998 - 1007

Published: Jan. 15, 2020

Language: Английский

---

Microbial-derived metabolites as a risk factor of age-related cognitive decline and dementia

Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)

Published: June 17, 2022

A consequence of our progressively ageing global population is the increasing prevalence worldwide age-related cognitive decline and dementia. In absence effective therapeutic interventions, identifying risk factors associated with becomes increasingly vital. Novel perspectives suggest that a dynamic bidirectional communication system between gut, its microbiome, central nervous system, commonly referred to as microbiota-gut-brain axis, may be contributing factor for health disease. However, exact mechanisms remain undefined. Microbial-derived metabolites produced in gut can cross intestinal epithelial barrier, enter systemic circulation trigger physiological responses both directly indirectly affecting functions. Dysregulation this (i.e., dysbiosis) modulate cytotoxic metabolite production, promote neuroinflammation negatively impact cognition. review, we explore critical connections microbial-derived (secondary bile acids, trimethylamine-N-oxide (TMAO), tryptophan derivatives others) their influence upon function neurodegenerative disorders, particular interest less-explored role decline.

Language: Английский

---

The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 298 - 328

Published: Oct. 17, 2022

Language: Английский

---

Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 75, P. 101573 - 101573

Published: Jan. 24, 2022

Indoleamine 2,3-dioxygenase 1 (IDO1) is activated in chronic inflammatory states, e.g., the aging process and age-related diseases. IDO1 enzyme catabolizes L-tryptophan (L-Trp) into kynurenine (KYN) thus stimulating KYN pathway. The depletion of L-Trp inhibits proliferation immune cells inflamed tissues it also reduces serotonin synthesis predisposing to psychiatric disorders. Interestingly, protein contains two immunoreceptor tyrosine-based inhibitory motifs (ITIM) which trigger suppressive signaling through binding PI3K p110 SHP-1 proteins. This immunosuppressive activity not dependent on catalytic IDO1. its metabolite, kynurenic acid (KYNA), are potent activators aryl hydrocarbon receptor (AhR) can enhance immunosuppression. IDO1-KYN-AhR counteracts excessive pro-inflammatory responses acute inflammation but states has many harmful effects. A low-grade associated with process, a state called inflammaging. There substantial evidence that activation pathway robustly increases process. does only suppress functions effector cells, probably promoting immunosenescence, impairs autophagy, induces cellular senescence, remodels extracellular matrix as well enhancing development osteoporosis vascular I will review function discuss an enhancer

Language: Английский

---

The Role of Tryptophan Metabolites in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(17), P. 9968 - 9968

Published: Sept. 1, 2022

In recent decades, neuropsychiatric disorders such as major depressive disorder, schizophrenia, bipolar, etc., have become a global health concern, causing various detrimental influences on patients. Tryptophan is an important amino acid that plays indisputable role in several physiological processes, including neuronal function and immunity. Tryptophan’s metabolism process the human body occurs using different pathways, kynurenine serotonin pathways. Furthermore, other biologically active components, serotonin, melatonin, niacin, are by-products of Current evidence suggests functional imbalance synthesis metabolites causes appearance pathophysiologic mechanisms leads to diseases. This review summarizes pharmacological tryptophan its development disorders. addition, quantification following neurotransmitters precursor highlighted. Eventually, efficiency biomarkers inflammatory, protein, electrophysiological, genetic, proteomic diagnosis/treatment was discussed understand biomarker application detection/treatment

Language: Английский

---