Establishment of a depression model using dexamethasone-treated three-dimensional cultured rat cortical cells DOI Creative Commons
Mi Kyoung Seo, Sehoon Jeong,

Woo Seok Cheon

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Abstract In vitro models are useful for exploring the molecular mechanisms underlying impaired neuroplasticity in depression. In this study, we developed a three-dimensional spheroid model using synthetic glucocorticoid dexamethasone to investigate its effects on key pathways involved neuroplasticity, specifically focusing BDNF, sirtuin 1, and mTORC1 signaling. A micro-spheroid device was fabricated photolithography soft lithography, cortical spheroids were generated from primary rat cells. These treated with varying concentrations of dexamethasone, their structure included neurons, astrocytes, microglia, oligodendrocytes. Dexamethasone treatment (100, 200, 300 µM) resulted dose-dependent reduction cell viability, BDNF mRNA expression, neurite outgrowth. At 100 µM, reduced expression 1 decreased phosphorylation ERK1/2. It also lowered levels mTORC1, 4E-BP1, p70S6K, as well synaptic proteins such PSD-95 GluA1. inhibited related neuroplasticity. While dexamethasone-treated may serve basis developing an in depression, further validation is required confirm broader applicability.

Language: Английский

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder DOI
Caroline M. Nievergelt, Adam X. Maihofer, Elizabeth G. Atkinson

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(5), P. 792 - 808

Published: April 18, 2024

Language: Английский

Citations

55
An Interaction between Brain-Derived Neurotrophic Factor and Stress-Related Glucocorticoids in the Pathophysiology of Alzheimer’s Disease DOI Open Access

Tadahiro Numakawa,

Ryutaro Kajihara

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1596 - 1596

Published: Jan. 27, 2024

Both the brain-derived neurotrophic factor (BDNF) and glucocorticoids (GCs) play multiple roles in various aspects of neurons, including cell survival synaptic function. BDNF its receptor TrkB are extensively expressed neurons central nervous system (CNS), contribution BDNF/TrkB to neuronal function is evident; thus, downregulation has been considered be involved pathogenesis Alzheimer’s disease (AD). GCs, stress-related molecules, glucocorticoid receptors (GRs) also associated with AD addition mental disorders such as depression. Importantly, a growing body evidence suggests close relationship between BDNF/TrkB-mediated signaling GCs/GR CNS. Here, we introduce current studies on interaction stress CNS discuss their involvement pathophysiology AD.

Language: Английский

Citations

11
How is prenatal stress transmitted from the mother to the fetus? DOI Creative Commons
Ying Sze, Paula J. Brunton

Journal of Experimental Biology, Journal Year: 2024, Volume and Issue: 227(Suppl_1)

Published: March 7, 2024

ABSTRACT Prenatal stress programmes long-lasting neuroendocrine and behavioural changes in the offspring. Often this programming is maladaptive sex specific. For example, using a rat model of maternal social late pregnancy, we have demonstrated that adult prenatally stressed male, but not female offspring display heightened anxiety-like behaviour, whereas both sexes show hyperactive hypothalamo–pituitary–adrenal (HPA) axis responses to stress. Here, review current knowledge mechanisms underpinning dysregulated HPA responses, including evidence supporting role for reduced neurosteroid-mediated GABAergic inhibitory signalling brains How psychosocial signalled from mother fetuses unclear. Direct transfer glucocorticoids often considered mediate effects on However, protective attenuated placental 11β-hydroxysteroid dehydrogenase-2 (which inactivates glucocorticoids) should limit materno-fetal glucocorticoid during pregnancy. Moreover, lack correlation between stress, circulating levels fetal reported several studies across different species. Therefore, here interrogate mediating consider alternative mechanisms, an indirect contribution placenta status fetus.

Language: Английский

Citations

9
Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids DOI Creative Commons
Leander Dony, Anthi C. Krontira,

Lea Kaspar

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(7)

Published: Feb. 14, 2025

Disruptions in the tightly regulated process of human brain development have been linked to increased risk for and mental illnesses. While genetic contribution these diseases is well established, important environmental factors less studied at molecular cellular levels. Here, we used single-cell cell type-specific techniques investigate effect glucocorticoid (GC) exposure, a mediator antenatal risk, on gene regulation lineage specification unguided neural organoids. We characterized transcriptional response chronic GC exposure during differentiation underlying regulatory networks by integrating transcriptomics with chromatin accessibility data. found lasting changes that included autism genes several transcription associated neurodevelopment. Chronic influenced primarily priming inhibitory neuron through like PBX3. provide evidence convergence common mechanism altering specification.

Language: Английский

Citations

1
An Update on the Psychiatric Genomics of Posttraumatic Stress Disorder (PTSD) DOI
Seth D. Norrholm

Psychiatric Clinics of North America, Journal Year: 2025, Volume and Issue: 48(2), P. 403 - 415

Published: March 4, 2025

Language: Английский

Citations

1
Depression risk in chronic tonsillitis patients underwent tonsillectomy: a global federated health network analysis DOI Creative Commons

Hui‐Chin Chang,

Hsin-Yo Lu, Yuchen Guo

et al.

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(5), P. 949 - 957

Published: Jan. 1, 2024

Background: Tonsillectomy is a common surgery in the US, with possible postoperative complications.While small studies indicate depressive symptoms may occur, large-scale evidence lacking on tonsillectomy-depression link.Methods: We conducted retrospective cohort study using TriNetX US collaborative network, offering de-identified electronic health data from 59 healthcare organizations (HCOs) United States.In this study, people being diagnosed of chronic tonsillitis between January 2005 and December 2017 were enrolled.Patients deceased, previous record cancers or psychiatric events before index date excluded.14,874 patients undergoing tonsillectomy propensity score matched 1:1 to controls for age, sex, race.New-onset depression risks evaluated over 5 years post-tonsillectomy stratified by age sex.Confounders adjusted including demographics, medications, comorbidities socioeconomic statuses.Results: After matching, difference key baseline characteristics comedications status obesity was insignificant non-tonsillectomy groups.Tonsillectomy had 1.29 times higher 5-year risk versus (95% CI, 1.19-1.40),with elevated seen at 1 year (HR=1.51;95% 1.28-1.79)and 3 (HR=1.30;95% 1.18-1.43).By stratifications, increased both males 1.08-1.57)and females 1.18-1.42),and significantly ages 18-64 (HR=1.37;1.26-1.49),but no significance observed those 65 older.After performing sensitivity analyses applying washout periods 6, 12, 36 months, outcome remained consistent unadjusted results. Conclusion:This real-world analysis found associated 30% tonsillitis.Further mechanistic research needed clarify pathophysiologic association tonsillectomy.Depression not commonly mentioned current care realm; however, our emphasized possibility these suffering condition after operation.Attention psychological impacts following warranted support patient well-being, leading better management individuals.

Language: Английский

Citations

4
Translational models of stress and resilience: An applied neuroscience methodology review DOI Creative Commons
Zeynep Seda Albayrak, Andreia Vaz, Joeri Bordes

et al.

Neuroscience Applied, Journal Year: 2024, Volume and Issue: 3, P. 104064 - 104064

Published: Jan. 1, 2024

Stress, encompassing psychological, physical, and physiological challenges, is an important factor affecting individual's well-being potentially leading to psychiatric, neurodegenerative, immune, metabolic disorders. However, not everyone exposed stress develops these conditions, highlighting the concept of resilience. Resilience a dynamic process categorized into four dimensions: pre-existing resilience capacity, ongoing processes, post-stress outcomes, recovery from psychopathologies. These dimensions involve genomic, cellular, systemic interactions influenced by genetic factors, early life experiences, adult experiences in addition community/environmental health behaviors. The biological response encompasses endocrine, autonomic, immunological, behavioral components, modulated stressor characteristics individual traits. Due limitations studying humans, translational models using rodents cell cultures are essential. Rodent include acute, chronic, traumatic paradigms, aiding study stress-related molecular outcomes. Additionally, models, such as prenatal maternal separation, provide insights developmental impacts. In this review, first, rodent for lifelong exposure will be summarized considering their validity, advantages, limitations. Subsequently, overview designed enhance capacity rodents, later employed outcomes given. Lastly, focus shifted culture iPSCs models. Finally, future considerations focused on improving used discussed. It aimed designs access more effective biomarkers associated with Stress complex phenomena various spanning levels. Integrating data across remains crucial unraveling complexities disorders

Language: Английский

Citations

4
Neurotoxic mechanisms of dexamethasone in SH-SY5Y neuroblastoma cells: Insights into bioenergetics, oxidative stress, and apoptosis DOI
Ekramy Elmorsy, Ayat B. Al‐Ghafari, Huda A. Al Doghaither

et al.

Steroids, Journal Year: 2024, Volume and Issue: unknown, P. 109514 - 109514

Published: Sept. 1, 2024

Language: Английский

Citations

4
Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids DOI Creative Commons
Leander Dony, Anthi C. Krontira,

Lea Kaspar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 22, 2024

Disruptions in the tightly regulated process of human brain development have been linked to increased risk for and mental illnesses. While genetic contribution these diseases is well established, important environmental factors less studied at molecular cellular levels. In this study, we used single-cell cell-type-specific techniques investigate effect glucocorticoid (GC) exposure, a mediator antenatal risk, on gene regulation lineage specification unguided neural organoids. We characterized transcriptional response chronic GC exposure during differentiation underlying regulatory networks by integrating transcriptomics-with chromatin accessibility data. found lasting cell type-specific changes that included autism genes several transcription associated with neurodevelopment. Chronic GCs influenced primarily priming inhibitory neuron through key like PBX3. provide evidence convergence common mechanism altering specification.

Language: Английский

Citations

3
Corticosteroid‐regulated gene transcription in SH‐SY5Y‐derived neurons: Insights into the mineralocorticoid and glucocorticoid receptor‐mediated response DOI Open Access

Justina F. Lugenbühl,

Clara Snijders,

Cameron D. Pernia

et al.

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Abstract Post‐traumatic stress disorder (PTSD) and major depressive (MDD) are debilitating stress‐related psychiatric disorders that can develop following exposure to traumatic events or chronic in some individuals. The neurobiological processes leading disease remain largely unknown. Among others, these characterized by a dysregulated hypothalamic–pituitary–adrenal axis, which is regulated the glucocorticoid receptor (GR) mineralocorticoid (MR). This leads altered downstream corticosteroid‐induced gene expression. In vitro models promising tools investigate specific underpinnings of response brain. Here, we investigated suitability SH‐SY5Y‐derived neurons as cost‐efficient system study role GR MR neuronal response. were characterized, exposed corticosteroids, analyzed on transcriptomic proteomic levels. We show (i) express sufficient seemingly functional allow transcription, (ii) three corticosteroids cortisol, dexamethasone, aldosterone, induced similar effects, (iii) antagonist spironolactone mildly attenuated effects dexamethasone FKBP5 , DUSP1 SUPV3L1 . Mifepristone did not significantly alter effect aldosterone. (iv) Integrating alterations corticosteroid‐exposed with those iPSC‐derived showed concordant two systems. To determine translational validity, compared expression transcriptome postmortem brain samples from individuals PTSD MDD, yielding stronger negative correlations corticosteroid signatures than MDD signatures. Upon further refinement validation, may serve simplistic tool implicated molecular networks around MR. Strengthening our insight into receptors' functions improves understanding commonly such MDD.

Language: Английский

Citations

0