Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration

Rivera, Andrea D.; Azim, Kasum; Macchi, Verónica; Porzionato, Andrea; Butt, Arthur M.; De, Raffaele

doi:10.3389/fncel.2022.838007

Cited by 13 publications

(5 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EGF exhibits neuroprotective effects against ischemic injury and prevents cerebrovascular damage [32]. Furthermore, EGF regulates oligodendrocyte progenitor cells, relevant to the remyelination capacity degradation in Alzheimer's disease or brain aging [33]. TRAF1 plays an important role in apoptosis and inflammatory responses in cerebral ischemia-reperfusion injuries [34].…”

Section: Discussionmentioning

confidence: 99%

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model

Kim,

Lim,

Cho

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

Vascular dementia (VD) is the second most prevalent dementia type, with no drugs approved for its treatment. Here, the effects of Banhabaekchulcheonma-Tang (BBCT) on ischemic brain injury and cognitive function impairment were investigated in a bilateral carotid artery stenosis (BCAS) mouse model. Mice were divided into sham-operated, BCAS control, L-BBCT (40 ml/kg), and H-BBCT (80 ml/kg) groups. BBCT's effects were characterized using the Y-maze test, novel object recognition test (NORT), immunofluorescence staining, RNA sequencing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analyses. The NORT revealed cognitive function improvement in the H-BBCT group, while the Y-maze test revealed no significant difference among the four groups. The CD68+ microglia and GFAP+ astrocyte numbers were reduced in the H-BBCT group. Furthermore, H-BBCT treatment restored the dysregulation of gene expression caused by BCAS. The major BBCT targets were predicted to be cell division cycle protein 20 (CDC20), Epidermal growth factor (EGF), and tumor necrosis factor receptor-associated factor 1 (TRAF1). BBCT regulates the neuroactive ligand-receptor interaction and neuropeptide signaling pathways, as predicted by KEGG and GO analyses, respectively. BBCT significantly improved cognitive impairment in a BCAS mouse model by inhibiting microglial and astrocyte activation and regulating the expression of CDC20, EGF, TRAF1, and key proteins in the neuroactive ligand-receptor interaction and neuropeptide signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model

Kim,

Lim,

Cho

et al. 2024

Int. J. Med. Sci.

View full text Add to dashboard Cite

show abstract

“…The ERBB/EGFR family of cell surface receptors represents another significant set of schizophrenia risk genes that act upstream to numerous biological processes and signalling pathways (comprehensively reviewed in [90]). The overactivation of ERBB/EGFR signalling at specific stages of the OL lineage precipitates programmed cell death/apoptosis and white matter loss, as indicated in previous studies ( [83,91,92]).…”

Section: Insights From Upstream Receptor Signalling To Intracellular ...mentioning

confidence: 99%

The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials

Rivera,

Normanton,

Butt

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to a potential reduction in life expectancy by up to 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying schizophrenia continue to remain enigmatic, with previous research yielding diverse and occasionally conflicting findings. Nonetheless, one consistently observed phenomenon in brain imaging studies of schizophrenia patients is the disruption of white matter, the bundles of myelinated axons that provide connectivity and rapid signalling between brain regions. Myelin is produced by specialised glial cells known as oligodendrocytes, which have been shown to be disrupted in post-mortem analyses of schizophrenia patients. Oligodendrocytes are generated throughout life by a major population of oligodendrocyte progenitor cells (OPC), which are essential for white matter health and plasticity. Notably, a decline in a specific subpopulation of OPC has been identified as a principal factor in oligodendrocyte disruption and white matter loss in the aging brain, suggesting this may also be a factor in schizophrenia. In this review, we analysed genomic databases to pinpoint intersections between aging and schizophrenia and identify shared mechanisms of white matter disruption and cognitive dysfunction.

show abstract

“…6i). The cognate receptor for NGF, NGFR, is expressed specifically in Oligodendrocytes and OPCs, suggesting partial disruption in communication with vulnerable Sst supertypes that may impact myelination [125][126][127] . MME encodes the protease Neprilysin that may break down Aβ peptides 128 , suggesting vulnerable Sst supertypes' may lose a critical mechanism for preventing later Aβ plaque formation near them.…”

Section: Vulnerable Sst Neurons In Early Admentioning

confidence: 99%

Integrated multimodal cell atlas of Alzheimer’s disease

Gabitto,

Travaglini,

Rachleff

et al. 2023

Preprint

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research atSEA-AD.org.

show abstract

Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration

Cited by 13 publications

References 93 publications

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model

Effects of Banhabaekchulcheonma-Tang on Brain Injury and Cognitive Function Impairment Caused by Bilateral Common Carotid Artery Stenosis in a Mouse Model

The Genomic Intersection of Oligodendrocyte Dynamics in Schizophrenia and Aging Unravels Novel Pathological Mechanisms and Therapeutic Potentials

Integrated multimodal cell atlas of Alzheimer’s disease

Contact Info

Product

Resources

About