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Interleukin-4 receptor signaling modulates neuronal network activity

ABSTRACT: Interleukin-4 receptor signaling modulates neuronal network activity

PROVIDER: PRJNA825260 | ENA |

REPOSITORIES: ENA

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Interleukin-4 receptor signaling modulates neuronal network activity [mouse]

Project description:Interleukin-4 receptor signaling modulates neuronal network activity [mouse]

| PRJNA825385 | ENA

Interleukin-4 receptor signaling modulates neuronal network activity

Project description:Neuroimmune interaction influences essential CNS processes. Hanuscheck et al. report expression of interleukin-4 receptor alpha at presynaptic terminals in mouse and human brain. Modulation of neuronal IL-R signaling alters the neuronal transcriptome, impacts synaptic transmission and causes anxiety-related behavior.

2022-04-13 | GSE200555 | GEO

Interleukin-4 receptor signaling modulates neuronal network activity [mouse]

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Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity

Project description:Nedd4-2 is an E3 ubiquitin ligase in which missense mutation is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2 and an isobaric labeling approach for quantitative comparison of the synaptic membrane proteome, we identified astrocytic channel proteins inwardly rectifying potassium channel 4.1 (Kir4.1) and Connexin43 as upregulated in ubiquitin ligase knockout mice and thus as candidate Nedd4-2 substrates. Kir4.1 and Connexin43 were confirmed as Nedd4-2 substrates by independent methods and their functional role in astrocytes as to modulation of neuronal network activity was established.

2023-11-28 | PXD046450 | Pride

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Lipid Accumulation Induced by APOE4 Impairs Microglial Surveillance of Neuronal-Network Activity

Project description:Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing late-onset Alzheimer’s disease and its expression in microglia is associated with pro-inflammatory states. How the interaction of APOE4 microglia with neurons differs from microglia expressing the disease-neutral allele APOE3 is currently unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect the impact of APOE4 in neuron-microglia communication. Our results reveal that APOE4 induces a distinct metabolic program in microglia that is marked by the accumulation of intracellular neutral lipid stores through impaired lipid catabolism. Importantly, this altered lipid-accumulated state shifts microglia away from homeostatic surveillance and renders APOE4 microglia weakly responsive to neuronal activity. By examining the transcriptional signatures of APOE3 versus APOE4 microglia before and after exposure to neuronal conditioned media, we further established that neuronal soluble cues differentially induce a lipogenic program in APOE4 microglia that exacerbates pro-inflammatory signals. Pharmacological blockade of lipogenesis in APOE4 microglia is sufficient to diminish intracellular lipid accumulation and restore microglial homeostasis. Remarkably, unlike APOE3 microglia that support neuronal network activity, co-culture of APOE4 microglia with neurons disrupts the coordinated activity of neuronal ensembles. We identified that through decreased uptake of extracellular fatty acids and lipoproteins, APOE4 microglia disrupts the net flux of lipids which results in decreased neuronal activity via the potentiation of the lipid-gated K+ channel, GIRK3. These findings suggest that neurological diseases that exhibit abnormal neuronal network-level disturbances may in part be triggered by impairment in lipid homeostasis in non-neuronal cells, underscoring a novel therapeutic route to restore circuit function in the diseased brain.

2022-05-19 | GSE203019 | GEO

Hypomorphic ASGR1 Modulates Lipid Homeostasis via SREBPs Network

Project description:Hypomorphic ASGR1 Modulates Lipid Homeostasis via SREBPs Network

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Lipid Accumulation Induced by APOE4 Impairs Microglial Surveillance of Neuronal-Network Activity

Project description:Lipid Accumulation Induced by APOE4 Impairs Microglial Surveillance of Neuronal-Network Activity

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Mitochondrial Network Organization during Neuronal Reprogramming, MT_UDF_WAX

Project description:The study focuses on an extensive biochemical fractionation with in-depth quantitative mass spectrometric profiling in the mitochondrial (mt) extracts of cultured human NTera2 embryonal carcinoma stem cells (i.e. ECSCs or undifferentiated state) and upon exposure to retinoic acid-induced differentiated neurons (DNs) to establish a network of high-quality mt protein-protein interactions. The resulting network showed that most of the native mt protein complexes with predicted subunits are previously unreported and endured extensive changes during neuronal differentiation and influence neuronal function and neurodegenerative disorder attributes.

2020-01-09 | PXD009832 | Pride

Mitochondrial Network Organization during Neuronal Reprogramming, MT_DF_SEC

2020-01-09 | PXD009833 | Pride

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