Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical and Translational Neuropsychiatry

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 574 - 574

Published: March 5, 2024

Neurodegeneration poses a significant challenge for the fields of neuroscience and medicine, as it is underlying cause development advancement numerous neurodegenerative psychiatric disorders [...]

Language: Английский

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Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

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From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment

Cells, Journal Year: 2023, Volume and Issue: 12(22), P. 2649 - 2649

Published: Nov. 17, 2023

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics management strategies migraines by targeting specific receptors neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors 56 71%. To address the need novel therapeutic targets, researchers are exploring potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as ground-breaking treatment avenue migraine. Preclinical models revealed how PACAP affects trigeminal system, which implicated in headache disorders. Clinical studies demonstrated significance migraine pathophysiology; however, few clinical trials remain inconclusive: 1 mAb, AMG 301 showed no benefit prevention, while ligand Lu AG09222 significantly reduced number monthly days over placebo phase 2 trial. Meanwhile, vasoactive intestinal (VIP) gaining interest new target. In light recent advances research, we emphasize promising target treatment, highlighting member antimigraine armamentarium, especially patients who do not respond or contraindicated anti-CGRP therapies. By updating our knowledge its unique contribution pathophysiology, pave way reinforcing other peptides, including VIP, option migraines.

Language: Английский

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Editorial: Case reports in neuroimaging and stimulation

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 2, 2023

EDITORIAL article Front. Psychiatry, 02 August 2023Sec. Neuroimaging Volume 14 - 2023 | https://doi.org/10.3389/fpsyt.2023.1264669

Language: Английский

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Editorial: Towards a mechanistic understanding of depression, anxiety, and their comorbidity: perspectives from cognitive neuroscience

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 15, 2023

EDITORIAL article Front. Behav. Neurosci., 15 August 2023Sec. Emotion Regulation and Processing Volume 17 - 2023 | https://doi.org/10.3389/fnbeh.2023.1268156

Language: Английский

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The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs on Motor Domain

Published: Feb. 20, 2024

The central nervous system (CNS) is the final frontier in drug delivery because of blood-brain barrier (BBB), which poses significant barriers to access most drugs their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role behavioral functions and abnormal KYNA levels have been observed neuropsychiatric conditions. current challenge lies delivering CNS owing its polar side chain. Recently, C-3 chain modified analogs shown cross BBB; however, it unclear whether they retain biological parent molecule. This study examined impact analogs, specifically SZR-72, SZR-104, newly developed SZRG-21, on behavior. were administered intracerebroventricularly (i.c.v.), effects motor domain compared with those KYNA. Specifically, open field (OF) rotarod (RR) tests employed assess activity skills. SZR-104 increased horizontal exploratory OF test at dose 0.04 μmol/4 μL, while SZR-72 decreased vertical doses 0.1 μL. In RR test, neither nor showed any differences skills either dose. Side modification affects affective performance behavior, as results show for first time. this study, we that alter emotional components such motor-associated curiosity emotions. Consequently, design necessitates development precise strategies traverse BBB paying close attention modifications

Language: Английский

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The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3394 - 3394

Published: March 16, 2024

The central nervous system (CNS) is the final frontier in drug delivery because of blood–brain barrier (BBB), which poses significant barriers to access most drugs their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role behavioral functions, and abnormal KYNA levels have been observed neuropsychiatric conditions. current challenge lies delivering CNS owing its polar side chain. Recently, C-3 chain-modified analogs shown cross BBB; however, it unclear whether they retain biological functions parent molecule. This study examined impact analogs, specifically, SZR-72, SZR-104, newly developed SZRG-21, on behavior. were administered intracerebroventricularly (i.c.v.), effects motor domain compared with those KYNA. Specifically, open-field (OF) rotarod (RR) tests employed assess activity skills. SZR-104 increased horizontal exploratory OF test at dose 0.04 μmol/4 μL, while SZR-72 decreased vertical doses 0.1 μL. In RR test, neither nor showed any differences skills either dose. Side chain modification affects affective performance behavior, as results show for first time. this study, we that alter emotional components such motor-associated curiosity emotions. Consequently, design necessitates development precise strategies traverse BBB paying close attention modifications

Language: Английский

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From Serendipity to Precision: Integrating AI, Multi-Omics, and Human-Specific Models for Personalized Neuropsychiatric Care

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 167 - 167

Published: Jan. 12, 2025

Background/Objectives: The dual forces of structured inquiry and serendipitous discovery have long shaped neuropsychiatric research, with groundbreaking treatments such as lithium ketamine resulting from unexpected discoveries. However, relying on chance is becoming increasingly insufficient to address the rising prevalence mental health disorders like depression schizophrenia, which necessitate precise, innovative approaches. Emerging technologies artificial intelligence, induced pluripotent stem cells, multi-omics potential transform this field by allowing for predictive, patient-specific interventions. Despite these advancements, traditional methodologies animal models single-variable analyses continue be used, frequently failing capture complexities human conditions. Summary: This review critically evaluates transition serendipity precision-based in research. It focuses key innovations dynamic systems modeling network-based approaches that use genetic, molecular, environmental data identify new therapeutic targets. Furthermore, it emphasizes importance interdisciplinary collaboration human-specific overcoming limitations Conclusions: We highlight precision psychiatry’s transformative revolutionizing care. paradigm shift, combines cutting-edge systematic frameworks, promises increased diagnostic accuracy, reproducibility, efficiency, paving way tailored better patient outcomes

Language: Английский

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From CGRP to PACAP: Unraveling the Next Chapter in Migraine Treatment

Published: Oct. 17, 2023

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics management strategies migraines by targeting specific receptors neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) receptor inhibitors remain around 50 percent. To address need novel therapeutic targets, researchers are exploring potential another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as ground-breaking treatment avenue migraine. Preclinical models have revealed how PACAP affects trigeminal system, which implicated in headache disorders. Clinical studies demonstrated significance migraine pathophysiology; however, few clinical trials inconclusive: 1 mAb, AMG 301 showed no benefit prevention, while ligand Lu AG09222 significantly reduced number monthly days over placebo phase 2 trial. Meanwhile, vasoactive intestinal (VIP) gaining interest new target. In light recent advances research, we emphasize promising target treatment, highlighting member antimigraine armamentarium, especially patients who do not respond to or contraindicated anti-CGRP therapies. By updating our knowledge its unique contribution pathophysiology, pave way reinforcing other peptides, including VIP, option migraines.

Language: Английский

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Magnetic resonance imaging–based machine learning classification of schizophrenia spectrum disorders: a meta‐analysis

Psychiatry and Clinical Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Background Recent advances in multivariate pattern recognition have fostered the search for reliable neuroimaging‐based biomarkers psychiatric conditions, including schizophrenia. These approaches consider complex of alterations brain function and structure, overcoming limitations traditional univariate methods. To assess reliability contribution study characteristics distinguishing individuals with schizophrenia spectrum disorder (SSD) from healthy controls (HCs), we conducted a systematic review studies that used this objective. Methods We systematically searched PubMed, Scopus, Web Science on SSD classification using analysis magnetic resonance imaging data. employed bivariate random‐effects meta‐analytic model to explore sensitivity (SE) specificity (SP) across while also evaluating moderator effects clinical non‐clinical variables. Results A total 119 (with 12,723 patients 13,196 HCs) were identified. The meta‐analysis estimated SE 79.1% (95% confidence interval [CI], 77.1%–81.0%) SP 80.0% CI, 77.8%–82.0%). In particular, Positive Negative Syndrome Scale Global Assessment Functioning scores, age, age onset, duration untreated psychosis, deep learning, algorithm type, features selection, validation methods had significant performance. Conclusions Multivariate reliably identifies SSD, achieving ∼80% SP. Despite heterogeneity, discernible modifications effectively differentiate HCs. Classification performance depends patient‐related methodological factors crucial development, validation, application prospective models settings.

Language: Английский

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