Scavenger Receptor-A deficiency impairs immune response of microglia and astrocytes potentiating Alzheimer’s disease pathophysiology

Cornejo, Francisca; Vruwink, Marianne; Metz, Claudia; Muñoz, Paola; Salgado, Nicole; Poblete, Joaquín; Andrés, Marı́a Estela; Eugenı́n, Jaime; Bernhardi, Rommy von

doi:10.1016/j.bbi.2017.12.007

Cited by 44 publications

(30 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, increased transcriptome variability of SCARA5 was observed in temporal cortex of autistic subjects [30]. We can speculate that this pathway participates in the crucial role of scavenger receptors in microglia inflammatory response, which is recognized in Alzheimer's disease [31,32], but is also important in MDD [33]; further studies are needed to confirm our results.…”

Section: Discussionsupporting

confidence: 53%

Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression

Carboni

Marchetti

Lauria

et al. 2018

Neuropsychopharmacol

View full text Add to dashboard Cite

An enhanced understanding of the pathophysiology of depression would facilitate the discovery of new efficacious medications. To this end, we examined hippocampal transcriptional changes in rat models of disease and in humans to identify common disease signatures by using a new algorithm for signature-based clustering of expression profiles. The tool identified a transcriptomic signature comprising 70 probesets able to discriminate depression models from controls in both Flinders Sensitive Line and Learned Helplessness animals. To identify disease-relevant pathways, we constructed an expanded protein network based on signature gene products and performed functional annotation analysis. We applied the same workflow to transcriptomic profiles of depressed patients. Remarkably, a 171-probesets transcriptional signature which discriminated depressed from healthy subjects was identified. Rat and human signatures shared the SCARA5 gene, while the respective networks derived from protein-based significant interactions with signature genes contained 25 overlapping genes. The comparison between the most enriched pathways in the rat and human signature networks identified a highly significant overlap (p-value: 3.85 × 10) of 67 terms including ErbB, neurotrophin, FGF, IGF, and VEGF signaling, immune responses and insulin and leptin signaling. In conclusion, this study allowed the identification of a hippocampal transcriptional signature of resilient or susceptible responses in rat MDD models which overlapped with gene expression alterations observed in depressed patients. These findings are consistent with a loss of hippocampal neural plasticity mediated by altered levels of growth factors and increased inflammatory responses causing metabolic impairments as crucial factors in the pathophysiology of MDD.

show abstract

Section: Discussionsupporting

confidence: 53%

Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression

Carboni

Marchetti

Lauria

et al. 2018

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Although we previously showed that LY379268 upregulates gene expression of SR CD36 in astrocytes [9], the literature points to class A SR (SR-A) as the central Aβ-interacting receptor in AD models. SR-A expression is reduced in the hippocampus of aged and APP/PS1 animals [11], and a triple transgenic APP/PS1/SR-A -/-mouse displays a reduced lifespan, reduced cognitive performance, and increased proinflammatory cytokine levels, as well as reduced microglial phagocytic capacity [11]. Consequently, these triple transgenic mice show accelerated Aβ accumulation, and pharmacological upregulation of SR-A expression on mononuclear phagocytes increases Aβ clearance [12].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

Durand

Turati

Rudi

et al. 2019

Neurochemistry International

Self Cite

View full text Add to dashboard Cite

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

show abstract

“…One of the most studied events of aging is the impairment of the immune system, characterized by an aberrant-increased activation of the innate immunity ( 214 , 215 ), and high levels of circulatory inflammatory mediators that establish an inflammatory environment, and a decrease of the adaptive immune response ( 216 , 217 ) and a decrease of the adaptive immune response ( 214 ) due to this low-grade chronic inflammation ( 214 , 218 ), which together would promote the inflammaging phenomenon ( 219 ). Interestingly, it is proposed that age would not be the cause per se of these diseases associated with aging ( 214 ).…”

Section: Aging Epigenetic and Immuno-inflammatory Imbalancementioning

confidence: 99%

“…Thus, these events could induce IL1β and TNFα release, changes in the chemoattraction of neutrophils mediated by the reduction of the intercellular adhesion molecule 1 (ICAM-1) expression, and the aberrant activation of the phosphoinositide lipid kinase-3 (PI3K) ( 235 ). Also, there is a decrease in the expression of pattern recognition receptors (PRR), which leads to the activation of proinflammatory signaling promoting tissue damage ( 215 , 216 ). Finally, the reduced level of certain hormones due to the impaired hypothalamic function causes the loss of muscle mass and an increase in adipose tissue, further contributing to the release of inflammatory cytokines and changes in metabolism ( 236 ).…”

Section: Aging Epigenetic and Immuno-inflammatory Imbalancementioning

confidence: 99%

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5–8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual’s sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging.

show abstract

Scavenger Receptor-A deficiency impairs immune response of microglia and astrocytes potentiating Alzheimer’s disease pathophysiology

Cited by 44 publications

References 93 publications

Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression

Cross-species evidence from human and rat brain transcriptome for growth factor signaling pathway dysregulation in major depression

Unraveling the β-amyloid clearance by astrocytes: Involvement of metabotropic glutamate receptor 3, sAPPα, and class-A scavenger receptor

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

Contact Info

Product

Resources

About