The combination of chronic stress and smoke exacerbated depression-like changes and lung cancer factor expression in A/J mice: Involve inflammation and BDNF dysfunction

Liu, Bai-Ping; Zhang, Cai; Zhang, Yongping; Li, Kang-Wei; Song, Cai

doi:10.1371/journal.pone.0277945

“…Chronic stress-induced depression-like behaviors are also associated with neuron apoptosis in mPFC and amygdala [24,25]. We found that KLK8 de ciency signi cantly attenuated CUMS-induced apoptosis in mPFC (supplemental Fig.…”

Section: Transgenic Overexpression Of Klk8 Exacerbates Whereas Klk8 D...mentioning

confidence: 71%

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Liu

¹

,

Xu

²

,

Du³

et al. 2023

Preprint

0

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Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.

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“…Chronic stress-induced depression-like behaviors are also associated with neuron apoptosis in mPFC and the amygdala [ 24 , 25 ]. We found that KLK8 deficiency significantly attenuated CUMS-induced apoptosis in mPFC (supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Xu¹,

Du²,

Liu³

et al. 2023

View full text Add to dashboard Cite

Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.

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“…30,31 Similar mechanisms were indicated by experiments in mice with lung cancer. 32 Alcohol exposure regulates gut microbiota and mediates anxiety and depression through NLRP3-mediated neuroinflammation. 33,34 This analysis not only illuminates the potential mechanisms affecting mental well-being but also provides valuable insights for clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“… 30 , 31 Similar mechanisms were indicated by experiments in mice with lung cancer. 32 Alcohol exposure regulates gut microbiota and mediates anxiety and depression through NLRP3‐mediated neuroinflammation. 33 , 34 …”

Section: Discussionmentioning

confidence: 99%

Screening for depression and anxiety in lung cancer patients: A real‐world study using GAD‐7 and HADS

Chau,

Zhou,

Chen

et al. 2024

Thoracic Cancer

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BackgroundThe psychological well‐being of lung cancer patients is critical in‐patient care but frequently overlooked.MethodsThis study, employing a cross‐sectional, questionnaire‐based design, aimed to elucidate the prevalence of depressive and anxiety symptoms among lung cancer patients and identify associated risk factors. Participants' demographic, medical history, disease stage, and pathology were systematically collected. Psychological assessment was conducted using the general anxiety disorder‐7 (GAD‐7), patient health questionnaire‐9 (PHQ‐9), and hospital anxiety and depression scale (HADS). Statistical analyses were performed using SPSS software (version 25.0).ResultsOut of 294 distributed questionnaires, 247 lung cancer patients were included in the final analysis, with an average completion time of 9.08 min. Notably, 32.4% exhibited depressive symptoms, while 30% displayed signs of anxiety. A significant correlation was found between both depressive and anxiety symptoms and a history of tobacco and alcohol consumption. Specifically, increased nicotine dependence and greater cumulative tobacco use were linked to higher rates of depressive symptoms, whereas cumulative alcohol consumption was associated with increased risks of anxiety symptoms.ConclusionThe study affirms the feasibility of GAD‐7, PHQ‐9, and HADS as screening tools for depressive and anxiety symptoms in lung cancer patients. It further highlights tobacco and alcohol consumption as significant risk factors for poor psychological health in this population.

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The combination of chronic stress and smoke exacerbated depression-like changes and lung cancer factor expression in A/J mice: Involve inflammation and BDNF dysfunction

Cited by 8 publications

References 91 publications

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Screening for depression and anxiety in lung cancer patients: A real‐world study using GAD‐7 and HADS

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