Precision Psychobiotics for Gut–Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy DOI Creative Commons
Rebecca F. Slykerman, Naomi Davies, Klára Vlčková

et al.

Microbial Biotechnology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 1, 2025

ABSTRACT Advancing microbiome–gut–brain axis science requires systematic, rational and translational approaches to bridge the critical knowledge gaps currently preventing full exploitation of gut microbiome as a tractable therapeutic target for gastrointestinal, mental brain health. Current research is still marked by many open questions that undermine widespread application humans. For example, lack mechanistic understanding probiotic effects means it remains unclear why even apparently closely related strains exhibit different in vivo. live microbial psychobiotics, consensus on their adjunct treatments conventional neuromodulators, use unmedicated populations or at‐risk cohorts with sub‐clinical symptomatology warranted. This missing information both sides equation when treating central nervous system (CNS) conditions makes psychobiotic challenging, especially compared other pharmaceutical functional food approaches. Expediting transition from positive preclinical data proven benefits humans includes interpreting promises pitfalls animal behavioural assays, well navigating mechanism‐informed decision making select right microbe(s) job. In this review, we consider how these decisions can be supported light accrued range clinical studies across healthy, pathological study populations, where specific have been evaluated context gastrointestinal physiology, function behaviour. Examples successful, partial unsuccessful translation bench bedside are considered. We also discuss developments silico analyses enhanced our moved towards pinpointing host–microbe interactions most important optimal gut–brain function. Combining assays vitro ex vivo domains incorporating model organisms prime discovery pipelines promising rationally selected candidates.

Language: Английский

Prefrontal cortex and depression DOI Open Access
Diego A. Pizzagalli, Angela Roberts

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(1), P. 225 - 246

Published: Aug. 2, 2021

Language: Английский

Citations

396
Reproducibility of animal research in light of biological variation DOI
Bernhard Voelkl, Naomi Altman, Anders Forsman

et al.

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(7), P. 384 - 393

Published: June 2, 2020

Language: Английский

Citations

306
Sex differences in anxiety and depression: circuits and mechanisms DOI
Debra A. Bangasser, Amelia Cuarenta

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(11), P. 674 - 684

Published: Sept. 20, 2021

Language: Английский

Citations

305
Microglial ERK-NRBP1-CREB-BDNF signaling in sustained antidepressant actions of (R)-ketamine DOI Creative Commons
Wei Yao, Qianqian Cao, Shilin Luo

et al.

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(3), P. 1618 - 1629

Published: Nov. 24, 2021

Abstract ( R,S )-ketamine elicits rapid-acting and sustained antidepressant actions in treatment-resistant patients with depression. R produces longer-lasting effects than S rodents; however, the precise molecular mechanisms underlying of remain unknown. Using isobaric Tag for Relative Absolute Quantification, we identified nuclear receptor-binding protein 1 (NRBP1) that could contribute to different antidepressant-like two enantiomers chronic social defeat stress (CSDS) model. NRBP1 was localized microglia neuron, not astrocyte, mouse medial prefrontal cortex (mPFC). increased expression NRBP1, brain-derived neurotrophic factor (BDNF), phosphorylated cAMP response element binding (p-CREB)/CREB ratio primary cultures thorough extracellular signal-regulated kinase (ERK) activation. Furthermore, activate BDNF transcription through activation CREB as well MeCP2 (methyl-CpG 2) suppression microglia. Single intracerebroventricular (i.c.v.) injection CREB-DNA/RNA heteroduplex oligonucleotides (CREB-HDO) or exon IV-HDO blocked CSDS susceptible mice. Moreover, microglial depletion by colony-stimulating receptor (CSF1R) inhibitor PLX3397 In addition, inhibition single i.c.v. mannosylated clodronate liposomes (MCLs) significantly Finally, CREB-HDO, MCLs beneficial on reduced dendritic spine density mPFC These data suggest a novel ERK-NRBP1-CREB-BDNF pathways )-ketamine.

Language: Английский

Citations

167
You’ve got male: Sex and the microbiota-gut-brain axis across the lifespan DOI
Minal Jaggar, Kieran Rea, Simon Spichak

et al.

Frontiers in Neuroendocrinology, Journal Year: 2019, Volume and Issue: 56, P. 100815 - 100815

Published: Dec. 2, 2019

Language: Английский

Citations

160
Animal Models of Depression: What Can They Teach Us about the Human Disease? DOI Creative Commons
Maria Becker, Albert Pinhasov, Asher Ornoy

et al.

Diagnostics, Journal Year: 2021, Volume and Issue: 11(1), P. 123 - 123

Published: Jan. 14, 2021

Depression is apparently the most common psychiatric disease among mood disorders affecting about 10% of adult population. The etiology and pathogenesis depression are still poorly understood. Hence, as for human diseases, animal models can help us understand and, more importantly, may facilitate search therapy. In this review we first describe tests used evaluation depressive-like symptoms in rodents. Then different discuss their strengths weaknesses. These be divided into several categories: genetic models, induced by mental acute chronic stressful situations caused environmental manipulations (i.e., learned helplessness rats/mice), changes brain neuro-transmitters or specific injuries pharmacological tools. spite fact that none completely resembles depression, relevant since they mimic many features observed situation serve a powerful tool study etiology, treatment especially only few patients respond to treatment. Relevance increases also has facets possible etiologies therapies.

Language: Английский

Citations

121
Future of Digital Assays to Resolve Clinical Heterogeneity of Single Extracellular Vesicles DOI
Renee‐Tyler T. Morales, Jina Ko

ACS Nano, Journal Year: 2022, Volume and Issue: 16(8), P. 11619 - 11645

Published: July 29, 2022

Extracellular vesicles (EVs) are complex lipid membrane vehicles with variable expressions of molecular cargo, composed diverse subpopulations that participate in the intercellular signaling biological responses disease. EV-based liquid biopsies demonstrate invaluable clinical potential for overhauling current practices disease management. Yet, EV heterogeneity is a major needle-in-a-haystack challenge to translate their use into practice. In this review, existing digital assays will be discussed analyze EVs at single vesicle resolution, and future opportunities optimize throughput, multiplexing, sensitivity highlighted. Furthermore, review outline challenges impact translation technologies diagnostics treatment monitoring.

Language: Английский

Citations

87
Sucrose Preference Test as a Measure of Anhedonic Behavior in a Chronic Unpredictable Mild Stress Model of Depression: Outstanding Issues DOI Creative Commons
Dmitrii D. Markov

Brain Sciences, Journal Year: 2022, Volume and Issue: 12(10), P. 1287 - 1287

Published: Sept. 24, 2022

Despite numerous studies on the neurobiology of depression, etiological and pathophysiological mechanisms this disorder remain poorly understood. A large number animal models tests to evaluate depressive-like behavior have been developed. Chronic unpredictable mild stress (CUMS) is most common frequently used model sucrose preference test (SPT) one for assessing anhedonia. However, not all laboratories can reproduce main effects CUMS, especially when refers a decrease in preference. It also unknown how state anhedonia, assessed by SPT, relates anhedonia patients with depression. We analyzed literature available PubMed database using keywords relevant topic narrative review. hypothesize that poor reproducibility CUMS may be due differences consumption, which influenced such factors as concentration threshold, water food deprivation, animals’ susceptibility stress. believe comparisons between human states should made caution because there are many inconsistencies two, including assessment methods. tried offer some recommendations improve provide framework future research.

Language: Английский

Citations

84
Rodent tests of depression and anxiety: Construct validity and translational relevance DOI Creative Commons

Sinem Gencturk,

Güneş Ünal

Cognitive Affective & Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 24(2), P. 191 - 224

Published: Feb. 27, 2024

Abstract Behavioral testing constitutes the primary method to measure emotional states of nonhuman animals in preclinical research. Emerging as characteristic tool behaviorist school psychology, behavioral animals, particularly rodents, is employed understand complex cognitive and affective symptoms neuropsychiatric disorders. Following symptom-based diagnosis model DSM, rodent models tests depression anxiety focus on patterns that resemble superficial these While practices provided researchers with a platform screen novel antidepressant anxiolytic drug candidates, their construct validity—involving relevant underlying mechanisms—has been questioned. In this review, we present laboratory procedures used assess depressive- anxiety-like behaviors rats mice. These include constructs rely stress-triggered responses, such despair, those emerge nonaversive training, bias. We describe specific are discuss criticisms theoretical background. review concerns about validity translational relevance individual tests, outline limitations traditional, interpretation, introduce novel, ethologically frameworks emphasize simple patterns. Finally, explore monitoring morphological analysis methods can be integrated into how they enhance tests.

Language: Английский

Citations

40
A consensus on the definition of positive animal welfare DOI Creative Commons
Jean‐Loup Rault, Melissa Bateson,

Alain Boissy

et al.

Biology Letters, Journal Year: 2025, Volume and Issue: 21(1)

Published: Jan. 1, 2025

The concept of animal welfare is evolving due to progress in our scientific understanding biology and changing societal expectations. Animal science has been primarily concerned with minimizing suffering, but there growing interest also promoting positive experiences, grouped under the term (PAW). However, are discrepancies use PAW. An interdisciplinary group arrived at a consensus that ‘PAW can be defined as flourishing through experience predominantly mental states development competence resilience. PAW goes beyond ensuring good physical health prevention alleviation suffering. It encompasses animals experiencing resulting from rewarding including having choices opportunities actively pursue goals achieve desired outcomes’. definition considers individual species-specific differences. provides framework for researchers investigate thereby generate innovative, informative reproducible science. Studies contribute richer picture an animal’s life may elucidate biological foundations happiness. creates inspire align care practices, legislation markets

Language: Английский

Citations

8