Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System

Cells, Год журнала: 2022, Номер 11(16), С. 2607 - 2607

Опубликована: Авг. 21, 2022

Nearly half a century has passed since the discovery of cytoplasmic inheritance human chloramphenicol resistance. The was then revealed to take place maternally by mitochondrial DNA (mtDNA). Later, number mutations in mtDNA were identified as cause severe inheritable metabolic diseases with neurological manifestation, and impairment functions been probed pathogenesis wide range illnesses including neurodegenerative diseases. Recently, growing preclinical studies have that animal behaviors are influenced possibly loss stress resilience. Indeed, high 54% patients one most common primary diseases, encephalomyopathy lactic acidosis stroke-like episodes (MELAS) syndrome, present psychiatric symptoms cognitive impairment, mood disorder, anxiety, psychosis. Mitochondria multifunctional organelles which produce cellular energy play major role other homeostasis, signaling, gene expression, among others. Mitochondrial observed be compromised become less resilient under continuous stress. Meanwhile, inflammation linked activation tryptophan (Trp)-kynurenine (KYN) system, observably contributes development pathological conditions disorders. This review discusses mitochondria Trp-KYN interaction system mitochondria, current understanding involvement clinical

Язык: Английский

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Characterizing cardiac autonomic dynamics of fear learning in humans

Psychophysiology, Год журнала: 2022, Номер 59(12)

Опубликована: Июнь 7, 2022

Understanding transient dynamics of the autonomic nervous system during fear learning remains a critical step to translate basic research into treatment fear-related disorders. In humans, it has been demonstrated that typically elicits heart rate deceleration. However, classical analyses variability (HRV) fail disentangle contribution parasympathetic and sympathetic systems, crucially, they are not able capture phasic changes learning. Here, gain deeper insight physiological underpinnings learning, novel frequency-domain analysis was performed using short-time Fourier transform, instantaneous spectral estimates extracted from point-process modeling algorithm. We tested whether components HRV, used as noninvasive probe mechanisms, can dissociate between conditioned neutral stimuli. found learned elicited deceleration in anticipation noxious Crucially, results revealed significant increase power high frequency band when facing stimulus, indicating increased (vagal) activity, which distinguished stimuli Our findings provide proximal measure involvement cardiac vagal psychophysiology extinction, thus offering new insights for characterization mental health illness.

Язык: Английский

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Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4114 - 4114

Опубликована: Фев. 18, 2023

Migraine and neuropathic pain (NP) are both painful, disabling, chronic conditions which exhibit some symptom similarities thus considered to share a common etiology. The calcitonin gene-related peptide (CGRP) has gained credit as target for migraine management; nevertheless, the efficacy applicability of CGRP modifiers warrant search more effective therapeutic targets management. This scoping review focuses on human studies pathogenic factors in NP, with reference available preclinical evidence explore potential novel targets. inhibitors monoclonal antibodies alleviate inflammation meninges; targeting transient receptor (TRP) ion channels may help prevent release nociceptive substances, modifying endocannabinoid system open path toward discovery analgesics. There exist tryptophan-kynurenine (KYN) metabolic system, is closely linked glutamate-induced hyperexcitability; alleviating neuroinflammation complement pain-relieving armamentarium, microglial excitation, observed conditions, be possible approach. Those several analgesic deserve explored analgesics; however, much remains missing. highlights need subtypes, TRP modulators, knowledge status KYN metabolites, consensus cytokines sampling, biomarkers function, innovative management methods NP.

Язык: Английский

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Neuropharmacological Modulation of N-methyl-D-aspartate, Noradrenaline and Endocannabinoid Receptors in Fear Extinction Learning: Synaptic Transmission and Plasticity

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5926 - 5926

Опубликована: Март 21, 2023

Learning to recognize and respond potential threats is crucial for survival. Pavlovian threat conditioning represents a key paradigm investigating the neurobiological mechanisms of fear learning. In this review, we address role specific neuropharmacological adjuvants that act on neurochemical synaptic transmission, as well brain plasticity processes implicated in memory. We focus novel manipulations targeting glutamatergic, noradrenergic, endocannabinoid systems, how modulation these systems affects extinction learning humans. show administration N-methyl-D-aspartate (NMDA) agonists system by fatty acid amide hydrolase (FAAH) inhibition can boost through stabilization regulation receptor concentration. On other hand, elevated noradrenaline levels dynamically modulate learning, hindering long-term processes. These pharmacological interventions could provide targeted treatments prevention strategies fear-based anxiety-related disorders.

Язык: Английский

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Fear-induced bradycardia in mental disorders: Foundations, current advances, future perspectives

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 149, С. 105163 - 105163

Опубликована: Апрель 6, 2023

Fear-induced bradycardia, a transient heart rate deceleration related to threatening event, is powerful technique used assess fear conditioning in humans. During the last century, studies highlighted its usefulness, even when applied patients with various psychiatric disorders. Here, we provide an insight into these first steps field as well modern works, which helped refining methodology. As data still limited, future endeavors will continue deepen knowledge on fear-induced bradycardia and ensure use biomarker expedite improve interventions, thus lowering socio-economic burden associated

Язык: Английский

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The Tryptophan-Kynurenine Metabolic System Is Suppressed in Cuprizone-Induced Model of Demyelination Simulating Progressive Multiple Sclerosis

Biomedicines, Год журнала: 2023, Номер 11(3), С. 945 - 945

Опубликована: Март 20, 2023

Progressive multiple sclerosis (MS) is a chronic disease with unique pattern, which histologically classified into the subpial type 3 lesions in autopsy. The lesion also homologous to that of cuprizone (CPZ) toxin-induced animal models demyelination. Aberration tryptophan (TRP)-kynurenine (KYN) metabolic system has been observed patients MS; nevertheless, KYN metabolite profile progressive MS remains inconclusive. In this study, C57Bl/6J male mice were treated 0.2% CPZ toxin for 5 weeks and then underwent 4 recovery. We measured levels serotonin, TRP, metabolites plasma brain samples at 1, 3, demyelination, 7 9 remyelination periods by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) after body weight measurement immunohistochemical analysis confirm development UHPLC-MS/MS measurements demonstrated significant reduction kynurenic acid, 3-hydoxykynurenine (3-HK), xanthurenic acid 3-HK, anthranilic week 5. Here, we show CPZ-induced mouse model Thus, potentially serves as biomarker thus opens new path toward planning personalized treatment, frequently obscured immunologic components deterioration.

Язык: Английский

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Preclinical modeling in depression and anxiety: Current challenges and future research directions

Advances in Clinical and Experimental Medicine, Год журнала: 2023, Номер 32(5), С. 505 - 509

Опубликована: Май 22, 2023

This editorial highlights the limitations of preclinical models in accurately reflecting complexity anxiety and depression, which leads to a lack effective treatments for these disorders. Inconsistencies experimental designs methodologies can entail conflicting or inconclusive findings, while an overreliance on medication mask underlying problems. Researchers are exploring new approaches modeling negative emotional disorders, including using patient-derived cells, developing more complex animal models, integrating genetic environmental factors. Advanced technologies, such as optogenetics, chemogenetics neuroimaging, also being employed improve specificity selectivity models. Collaboration innovation across different disciplines sectors needed address societal challenges, requires funding support that prioritize cooperation multidisciplinary research. By harnessing power technology ways working, researchers collaborate effectively bring about transformative change.

Язык: Английский

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Targeting Human Glucocorticoid Receptors in Fear Learning: A Multiscale Integrated Approach to Study Functional Connectivity

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 864 - 864

Опубликована: Янв. 10, 2024

Fear extinction is a phenomenon that involves gradual reduction in conditioned fear responses through repeated exposure to fear-inducing cues. Functional brain connectivity assessments, such as functional magnetic resonance imaging (fMRI), provide valuable insights into how regions communicate during these processes. Stress, ubiquitous aspect of life, influences learning and by changing the activity amygdala, prefrontal cortex, hippocampus, leading enhanced and/or impaired extinction. Glucocorticoid receptors (GRs) are key stress response show dual function regulation: while they enhance consolidation memories, also facilitate Accordingly, GR dysregulation associated with anxiety mood disorders. Recent advancements cognitive neuroscience underscore need for comprehensive understanding integrates perspectives from molecular, cellular, systems levels. In particular, neuropharmacology provides neurotransmitter receptor systems, aiding investigation mechanisms underlying regulation potential therapeutic targets. A notable player this context cortisol, hormone, which significantly both memory reconsolidation Gaining thorough intricate interactions has implications terms addressing psychiatric disorders related stress. This review sheds light on complex between processes, emotions, their neural bases. endeavor, our aim reshape comprehension fear, stress, emotional well-being, ultimately development interventions.

Язык: Английский

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Neural Correlates and Molecular Mechanisms of Memory and Learning

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(5), С. 2724 - 2724

Опубликована: Фев. 27, 2024

Memory and learning are essential cognitive processes that enable us to obtain, retain, recall information [...].

Язык: Английский

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Genetic differences associated with dopamine and serotonin release mediate fear-induced bradycardia in the human brain

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 15, 2024

Abstract Fear-induced bradycardia, a transient heartbeat deceleration following exposure to threat, is physiological index observable in humans, especially fear conditioning experiments. While gaining interest recent years, it still currently underemployed neuroscientific research compared more popular indices. Besides its use research, could also constitute valuable resource clinical psychiatry setting, as many disorders are characterized by altered heart rate responses. However, differences fear-induced bradycardia may be subtended genetic interindividual differences, thus suggesting precaution when recommending the setting. Here, we discussed first endeavors that aimed at clarifying underpinnings of variations, which suggest individual have role defining characteristics Given this, translating measurements setting must implemented with caution. Future this field will aim identifying these even further, allowing for precise interventions.

Язык: Английский

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