FAAH Inhibition Reverses Depressive-like Behavior and Sex-Specific Neuroinflammatory Alterations Induced by Early Life Stress DOI Creative Commons

Anna Portugalov,

Irit Akirav

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1881 - 1881

Published: Nov. 14, 2024

Early life stress (ELS) increases predisposition to major depressive disorder (MDD), with neuroinflammation playing a crucial role. This study investigated the long-term effects of fatty acid amide hydrolase (FAAH) inhibitor URB597 on ELS-induced depressive-like behavior and messenger RNA (mRNA) pro-inflammatory cytokines in medial prefrontal cortex (mPFC) CA1 regions. We also assessed whether these gene expression alterations were present at onset treatment during late adolescence. ELS induced phenotype adult male female rats, which was reversed by URB597. In mPFC, downregulated nuclear factor kappa B1 (nfκb1) both sexes, while normalized this exclusively males. females, interleukin (il) 6 tumor necrosis alpha (tnfα) but upregulated il1β corticotropin-releasing (crf); il6, il1β, crf. CA1, tnfα males Some began adolescence, including mPFC-nfκb1 mPFC-il6 mPFC-il1β CA1-il1β CA1-tnfα males, females. These findings highlight as therapeutic approach for reversing associating changes neuroinflammatory cytokines, notable sex differences.

Language: Английский

Recognizing depression as an inflammatory disease: The search for endotypes DOI
Johannes Steffen, Nis Focken, Gürsel Çalışkan

et al.

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(1), P. C205 - C212

Published: June 3, 2024

Major depressive disorder (MDD) affects millions of individuals worldwide, leading to considerable social and economic costs. Despite advancements in pharmacological treatments, achieving remission remains a key challenge, with substantial number patients showing resistance existing therapies. This is often associated elevated levels proinflammatory cytokines, suggesting connection between inflammation, MDD pathophysiology, treatment efficacy. The observation increased immune activation about quarter resulted the distinction inflammatory noninflammatory endotypes. Although anti-inflammatory treatments show promise alleviating depression-like symptoms, responses are heterogeneous, thus highlighting importance identifying distinct endotypes tailor effective therapeutic strategies. intestinal microbiome emerges as crucial modulator mental health, mediating its effects partially through different pathways. Microbiota-derived short-chain fatty acids (SCFAs) significantly impact innate adaptive cells, regulating their differentiation, function, cellular response. Furthermore, gut-educated cells reach border regions central nervous system (CNS), glial cell functions. CNS modulates via efferent parts vagus nerve, afferent tracts concurrently transport information on peripheral inflammation back brain. bidirectional communication particularly relevant depression, allowing for stimulation nerve context depression In this review, we explore intricate relationship discuss how signals translated into depressive-like highlight immune-modulating avenues.

Language: Английский

Citations

9
Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms DOI Creative Commons
Luisa Speranza, Kardelen Dalım Filiz, Pellegrino Lippiello

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1978 - 1978

Published: Sept. 2, 2024

Stress profoundly affects physical and mental health, particularly when experienced early in life. Early-life stress (ELS) encompasses adverse childhood experiences such as abuse, neglect, violence, or chronic poverty. These stressors can induce long-lasting changes brain structure function, impacting areas involved emotion regulation, cognition, response. Consequently, individuals exposed to high levels of ELS are at an increased risk for health disorders like depression, anxiety, post-traumatic disorders, well issues, including metabolic cardiovascular disease, cancer. This review explores the biological psychological consequences early-life adversity paradigms rodents, maternal separation deprivation limited bedding nesting. The study these experimental models have revealed that organism’s response is complex, involving genetic epigenetic mechanisms, associated with dysregulation physiological systems nervous, neuroendocrine, immune systems, a sex-dependent fashion. Understanding impact crucial developing effective interventions preventive strategies humans stressful traumatic childhood.

Language: Английский

Citations

6
Apoptosis-induced decline in hippocampal microglia mediates the development of depression-like behaviors in adult mice triggered by unpredictable stress during adolescence DOI
Hao‐Jie Zhu,

Hainan Pan,

Yunli Fang

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176763 - 176763

Published: June 20, 2024

Language: Английский

Citations

4
Early life stress and brain development: Neurobiological and behavioral effects of chronic stress DOI
Subia Jamil, Muhammad Liaquat Raza, Nasrollah Moradikor

et al.

Progress in brain research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
HPA axis in psychotic and non-psychotic major depression: Cortisol plasma levels and hippocampal volume DOI Creative Commons
Ulrich Rabl, Lucie Bartova,

Patrick Sezen

et al.

Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Neonatal maternal separation causes depressive-like behavior and potentiates memory impairment induced by amyloid-β oligomers in adult mice DOI Creative Commons
Patrick Remus Suman, Grasielle C. Kincheski, Rudimar Luiz Frozza

et al.

Behavioral and Brain Functions, Journal Year: 2025, Volume and Issue: 21(1)

Published: March 20, 2025

Alzheimer's disease (AD) is characterized by memory decline and mood alterations. A growing body of evidence implicates stress other social determinants health as potential contributors to the progressive cerebral alterations that culminate in AD. In current study, we investigated impact neonatal maternal separation (MS) on susceptibility male female mice AD-associated impairments depressive-like behavior adulthood, brain levels pro-inflammatory cytokines neurotransmitters. Male Swiss were exposed MS for 180 min daily from post-natal day 1 10. Seventy days post-MS, received an intracerebroventricular infusion amyloid-β oligomers (AβOs), evaluated. Levels TNF-α, IL-1β, serotonin, dopamine, related metabolites determined cortex hippocampus. Previous exposure alone did not cause adult mice. Interestingly, however, increased impairment induced AβOs, potentiated inhibitory AβOs females. Females more susceptible caused a low dose regardless MS. No changes IL-1β found. decrease TNF-α was selectively found females pmol AβOs. led increase serotonin (5-HT) hippocampus mice, without influencing metabolite, 5-HIAA. Changes turnover predominantly observed dopamine or its Neonatal enhances cognitive deficits sex-specific manner. This suggests early life may play role development

Language: Английский

Citations

0
Cortisol, Behavior, and Victims of Intimate Partner Violence DOI

Sarai Mata Gil,

J. Martínez, Antonio Sánchez Cabaco

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Tau and Depression: A Systematic Review DOI Open Access
Juliano Flávio Rubatino Rodrigues,

Lívia Rodrigues,

Franciany Rodrigues

et al.

Published: Aug. 13, 2024

Objectives: The tau protein is essential for stabilizing microtubules. Changes in its phosphorylation are identified many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. hyperphosphorylation of the linked to various factors, including stress, which has a substantial impact on depressive illness. present study aimed systematically review studies that describe association between depression.Design: used PRISMA statement 2020 inclusion criterion articles describing individuals with depression. exclusion was lack comparison levels without depression.Results: A total 138 papers were identified, 21 ultimately included. One out every three included demonstrated statistical significance values depression group controls. Only one had an adequate sample but results any major significance.Conclusions: remains unclear. Studies sampling necessary answer this question.

Language: Английский

Citations

2
FAAH Inhibition Reverses Depressive-like Behavior and Sex-Specific Neuroinflammatory Alterations Induced by Early Life Stress DOI Creative Commons

Anna Portugalov,

Irit Akirav

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1881 - 1881

Published: Nov. 14, 2024

Early life stress (ELS) increases predisposition to major depressive disorder (MDD), with neuroinflammation playing a crucial role. This study investigated the long-term effects of fatty acid amide hydrolase (FAAH) inhibitor URB597 on ELS-induced depressive-like behavior and messenger RNA (mRNA) pro-inflammatory cytokines in medial prefrontal cortex (mPFC) CA1 regions. We also assessed whether these gene expression alterations were present at onset treatment during late adolescence. ELS induced phenotype adult male female rats, which was reversed by URB597. In mPFC, downregulated nuclear factor kappa B1 (nfκb1) both sexes, while normalized this exclusively males. females, interleukin (il) 6 tumor necrosis alpha (tnfα) but upregulated il1β corticotropin-releasing (crf); il6, il1β, crf. CA1, tnfα males Some began adolescence, including mPFC-nfκb1 mPFC-il6 mPFC-il1β CA1-il1β CA1-tnfα males, females. These findings highlight as therapeutic approach for reversing associating changes neuroinflammatory cytokines, notable sex differences.

Language: Английский

Citations

1