Weighted gene co-expression identification of CDKN1A as a hub inflammation gene following cardiopulmonary bypass in children with congenital heart disease

Chen, Huan; Liu, Jinglan; Wu, Yuqing; Jiang, Li; Wang, Xin; Fang, Xiaoling; Wang, Xi

doi:10.3389/fsurg.2022.963850

Cited by 4 publications

(2 citation statements)

References 47 publications

(48 reference statements)

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“…S100A9 activates NF-κB signaling and has been shown to aggravate neuroinflammation in a model of subarachnoid hemorrhage 108 and Alzheimer’s disease 109 and has been implicated as an integral component of inflammation along the gut-brain axis in the DSS model 15 . Cyclin-dependent kinase inhibitor p21, encoded by Cdkn1a , appears to be an inflammatory response element and may be a marker of DNA damage 110,111 , and an upregulation of the IL-1 receptor type 1, encoded by Il1r1 , has been associated with pathogenesis in several neurodegenerative diseases 112 . In general, the colitis-induced neuroimmune response is complex, and further work will be needed to unravel this complexity especially amidst LC injury.…”

Section: Discussionmentioning

confidence: 99%

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Boles,

Holt,

Cole

et al. 2024

Preprint

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Parkinson's disease (PD) is characterized by a decades-long prodrome, consisting of a collection of non-motor symptoms that emerges prior to the motor manifestation of the disease. Of these non-motor symptoms, gastrointestinal dysfunction and deficits attributed to central norepinephrine (NE) loss, including mood changes and sleep disturbances, are frequent in the PD population and emerge early in the disease. Evidence is mounting that injury and inflammation in the gut and locus coeruleus (LC), respectively, underlie these symptoms, and the injury of these systems is central to the progression of PD. In this study, we generate a novel two-hit mouse model that captures both features, using dextran sulfate sodium (DSS) to induce gut inflammation and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to lesion the LC. We first confirmed the specificity of DSP-4 for central NE using neurochemical methods and fluorescence light-sheet microscopy of cleared tissue, and established that DSS-induced outcomes in the periphery, including weight loss, gross indices of gut injury and systemic inflammation, the loss of tight junction proteins in the colonic epithelium, and markers of colonic inflammation, were unaffected with DSP-4 pre-administration. We then measured alterations in neuroimmune gene expression in the ventral midbrain in response to DSS treatment alone as well as the extent to which prior LC injury modified this response. In this two-hit model we observed that DSS-induced colitis activates the expression of key cytokines and chemokines in the ventral midbrain only in the presence of LC injury and the typical DSS-associated neuroimmune is blunted by pre-LC lesioning with DSP-4. In all, this study supports the growing appreciation for the LC as neuroprotective against inflammation-induced brain injury and draws attention to the potential for NEergic interventions to exert disease-modifying effects under conditions where peripheral inflammation may compromise ventral midbrain dopaminergic neurons and increase the risk for development of PD.

show abstract

Section: Discussionmentioning

confidence: 99%

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Boles,

Holt,

Cole

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…S100A9 activates NF-κB signaling and has been shown to aggravate neuroin ammation in a model of subarachnoid hemorrhage 108 and Alzheimer's disease 109 and has been implicated as an integral component of in ammation along the gut-brain axis in the DSS model 15 . Cyclindependent kinase inhibitor p21, encoded by Cdkn1a, appears to be an in ammatory response element and may be a marker of DNA damage 110,111 , and an upregulation of the IL-1 receptor type 1, encoded by Il1r1, has been associated with pathogenesis in several neurodegenerative diseases 112 . In general, the colitis-induced neuroimmune response is complex, and further work will be needed to unravel this complexity especially amidst LC injury.…”

Section: Discussionmentioning

confidence: 99%

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Tansey,

Boles,

Holt

et al. 2024

Preprint

View full text Add to dashboard Cite

Parkinson’s disease (PD) is characterized by a decades-long prodrome, consisting of a collection of non-motor symptoms that emerges prior to the motor manifestation of the disease. Of these non-motor symptoms, gastrointestinal dysfunction and deficits attributed to central norepinephrine (NE) loss, including mood changes and sleep disturbances, are frequent in the PD population and emerge early in the disease. Evidence is mounting that injury and inflammation in the gut and locus coeruleus (LC), respectively, underlie these symptoms, and the injury of these systems is central to the progression of PD. In this study, we generate a novel two-hit mouse model that captures both features, using dextran sulfate sodium (DSS) to induce gut inflammation and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to lesion the LC. We first confirmed the specificity of DSP-4 for central NE using neurochemical methods and fluorescence light-sheet microscopy of cleared tissue, and established that DSS-induced outcomes in the periphery, including weight loss, gross indices of gut injury and systemic inflammation, the loss of tight junction proteins in the colonic epithelium, and markers of colonic inflammation, were unaffected with DSP-4 pre-administration. We then measured alterations in neuroimmune gene expression in the ventral midbrain in response to DSS treatment alone as well as the extent to which prior LC injury modified this response. In this two-hit model we observed that DSS-induced colitis activates the expression of key cytokines and chemokines in the ventral midbrain only in the presence of LC injury and the typical DSS-associated neuroimmune is blunted by pre-LC lesioning with DSP-4. In all, this study supports the growing appreciation for the LC as neuroprotective against inflammation-induced brain injury and draws attention to the potential for NEergic interventions to exert disease-modifying effects under conditions where peripheral inflammation may compromise ventral midbrain dopaminergic neurons and increase the risk for development of PD.

show abstract

Bioinformatic analysis identifies GPR91 as a potential key gene in brain injury after deep hypothermic low flow

Puwei¹,

Ma²,

ZhuoGa³

et al. 2023

Heliyon

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Weighted gene co-expression identification of CDKN1A as a hub inflammation gene following cardiopulmonary bypass in children with congenital heart disease

Cited by 4 publications

References 47 publications

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Locus coeruleus injury modulates ventral midbrain neuroinflammation during DSS-induced colitis

Bioinformatic analysis identifies GPR91 as a potential key gene in brain injury after deep hypothermic low flow

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