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Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

ABSTRACT: Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

PROVIDER: PRJNA1010768 | ENA |

REPOSITORIES: ENA

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Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

Project description:Objective: The aim of this study was to identify the neural and molecular mechanisms underlying the comorbidity of rheumatoid arthritis (RA) and depression. Methods: A cohort of 200 RA patients were recruited to quantitatively assess the association between depressive symptoms and RA disease activity, as well as quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA was used to screen for brain regions that showed changes in c-FOS expression, an indicator of alteration in brain activity, accompanying the appearance of depression-like behaviors. RNA sequencing, immunostaining, AAV-mediated expression, micro-CT, plasma cytokines/chemokines measurements and histological analyses were applied to evaluate the contribution of the identified brain region in the disease progression of RA and depression-like symptoms. Results: In this study, we showed that in RA patients, the depression scores were significantly correlated with the severity and quality of life of the patients. The CAIA mice developed RA symptoms, together with depression-like behaviors accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region processing negative valence. Importantly, inhibition of the LHb outputs not only alleviated depression-like behaviors, but also resulted in rapid remission of RA symptoms and reduction in sympathetic nerve fibers in the synovial joints of the CAIA mice.Conclusion: Our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

2025-08-30 | GSE241929 | GEO

Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

Project description:In this study, we established mice with orthotopic colorectal cancer (CRC mice) and observed depression-like behaviors in the CRC mice. Through whole-brain c-FOS mapping, functional connectivity analysis, gut-brain inverse mapping, and correlation analysis, combined with chemogenetic manipulation, we identified the anterior cingulate cortex (ACC) as a key hub in the depression-related brain network. we performed whole transcriptome sequencing of key neural nuclei to identify molecular changes associated with CRC-depression comorbidity. Furthermore, chemogenetic modulation of neuronal excitability not only alleviated depression-like behavior but also reduced CRC progression in these mice. Importantly, our findings suggest that targeting the ACC, in addition to conventional colorectal cancer therapies, could offer therapeutic and quality-of-life benefits for patients with both CRC and depression.

2024-11-20 | GSE281840 | GEO

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

Project description:While depression and chronic pain are frequently comorbid, underlying neuronal circuits, and their relevance for the understanding of psychopathology, remain poorly defined. Here we show in mice that hyperactivity of the neuronal pathway linking the basolateral amygdala to the anterior cingulate cortex is essential for chronic pain-induced depression. In naive male mice, we demonstrate that activation of this pathway is sufficient to trigger depressive-like behaviors, as well as transcriptomic alterations that recapitulate core molecular features of depression in the human brain. These alterations notably impact gene modules related to myelination and the oligodendrocyte lineage. Among these, we show that Sema4a, a hub gene significantly upregulated in both male mice and humans in the context of altered mood, is necessary for the emergence of depressive-like behaviors. Overall, these results place the BLA-ACC pathway at the core of pain and depression comorbidity, and unravel the role of impaired myelination and Sema4a in mood control.

2023-04-26 | GSE227159 | GEO

Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

Project description:Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

| PRJNA1185799 | ENA

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

Project description:The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

| PRJNA943487 | ENA

Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (mRNA)

Project description:After intarvenouse catheter surgery, nicotine self-administration using an operant self-administration chamber, was conducted for 44 days with various doses of nicotine solution. Age-matched mice were used for control. After the self-administration, the Lateral Habenual (LHb) and the Medial Habenula (MHb) of the mouse brain were collected. We used microarrays to detail the mRNA expression profile of the Lateral Habenual (LHb) and the Medial Habenula (MHb) after the nicotine self-administration.

2015-03-04 | E-GEOD-66451 | biostudies-arrayexpress

Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

Project description:Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

| PRJNA563337 | ENA

Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix

Project description:We performed RNA-seq in lateral habenula of mice with susceptibility to chronic social defeat stress.

2020-08-28 | GSE156965 | GEO

Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

Project description:Chronic stress (CMS) affects many brain functions and is a major risk factor for the development of depression. Here, we demonstrate that CMS-induced hyperactivity in VTA-projecting lateral habenula (LHb) neurons is associated with increased passive coping (PC) but not anxiety or anhedonia. LHb→VTA neurons in mice with increased PC show increased burst and tonic firing as well as synaptic adaptations in excitatory inputs from the entopeduncular nucleus (EP). In-vivo manipulations of EP→LHb or LHb→VTA neurons selectively alter PC and effort-related motivation. Conversely, dorsal raphe (DR)-projecting LHb neurons do not show CMS-induced hyperactivity and are targeted indirectly by the EP. Using single-cell transcriptomics we reveal a set of genes that can collectively serve as biomarkers to identify mice with increased PC and differentiate LHb→VTA from LHb→DR neurons. Together, we provide a set of biological markers at the level of genes, synapses, cells and circuits that define a distinctive CMS-induced behavioral phenotype.

2019-09-16 | GSE136723 | GEO

Light augments antidepressant response via astroglial modulation of lateral habenula

Project description:Successful antidepressant treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate, using a new mouse model of depression resistant to antidepressants including ketamine, that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevented the potentiating effect of BLS on the antidepressant response. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and 5-HT tone as crucial buffer systems.

2025-03-12 | GSE143820 | GEO

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