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Astrocyte Fabp7 modulates seizure threshold and activity-dependent gene expression in mouse brain

ABSTRACT: Astrocyte Fabp7 modulates seizure threshold and activity-dependent gene expression in mouse brain

PROVIDER: PRJNA1134245 | ENA |

REPOSITORIES: ENA

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Astrocyte Fabp7 modulates seizure threshold and activity-dependent gene expression in mouse brain

Project description:Patients with epilepsy often experience increased frequency of seizures at night. Given the crucial role glial cells play in modulating neuronal excitability, we hypothesize that circadian changes in glia may affect changes in seizure threshold. Fatty acid binding protein 7 (Fabp7) is expressed in brain astrocytes and is involved in the transport of fatty acids, signal transduction, and gene transcription. Its mRNA expression levels rise and fall in a circadian rhythm and is necessary for normal sleep regulation. We examined if Fabp7 influences electrically induced seizure threshold and differential gene expression in wild type (WT) vs. Fabp7 knockout (KO) mice with and without seizure.

2024-11-06 | GSE271985 | GEO

Comprehensive transcriptome analysis of the cochleae of 7-month-old Fabp7 (+/+) and Fabp7 (-/-) mice

Project description:To discover the molecules and signal pathways that are associated with the anti-aging effects of Fabp7 deficiency, transcriptome analyses were conducted using DNA microarray. The ABR thresholds of Fabp7 (+/+) and Fabp7 (-/-) mice were not significantly different at 7 months of age, but it was speculated that important gene expression changes might arise at approximately this stage. Therefore, 7-month-old Fabp7 (+/+) and Fabp7 (-/-) mice were used for transcriptome analyses.

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FABP7 drives an inflammatory response in human astrocytes

Project description:To investigate the effect of FABP7 over-expression in human iPCS-derived astrocytes.

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Transcriptome Analysis of Differentially Expressed Genes in the Wild-type and Fabp7 KO Mouse Inner Ear

Project description:To reveal the function of FABP7 in the inner ear, we evaluated gene expressions between Wild-type and Fabp7 KO mice one day after noise exposure at 10 weeks, using RNA sequencing analysis. The read number was approximately 27–32 million paired-end reads per sample. A total of 24 and 23 genes were identified as upregulated and downregulated differentially expressed genes (DEGs), respectively in Fabp7 KO mice. The upregulation of genes related to nicotinamide-adenine dinucleotide (NADH) dehydrogenase (mt-Nd1, 2, 3, 4, and 6) and a glial high-affinity glutamate transporter (solute carrier family 1, member 2: Slc1a2) and downregulation of genes related to C/D box small nucleolar RNAs were observed in Fabp7 KO mice.

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Identification and analysis of differently expressed genes in liver macrophages from WT and FABP7 KO mice with MC38 metastatic.

Project description:Studies have shown that FABP7 is involved in the occurrence and development of various tumors and can serve as a prognostic marker for tumors. But, the function and molecular mechanism of FABP7 in the tumor microenvironment have not been reported.

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Expression of the neuronal tRNA n-Tr20 regulates synaptic transmission and seizure susceptibility

Project description:Loss of the nuclear-encoded brain-specific arginine UCU tRNA, n-Tr20, gene increases seizure threshold in mice, and alters inhibitory neurotransmission in the hippocampus. We investigated the molecular impact of loss of n-Tr20 expression on the trancriptome and translatome in the forebrain and hippocampus of multiple n-Tr20 mutant and control strains. Loss of n-Tr20 altered translation initiation by activating the integrated stress response and suppressing mTOR signaling, the latter of which contributes to the enhanced GABAergic transmission.

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Astrocyte proximity modulates the myelination gene fabric of oligodendrocytes

Project description:Extensive literature documented that astrocytes release neurotransmitters, cytokines and other signaling molecules that modulate migration, maturation and myelin synthesis of oligodendrocytes through mechanisms primarily converging on cytosolic [Ca2+] transients. Considering the long term effects, it is expected that astrocyte conditioned medium is a major regulator of gene expression in oligodendrocytes even in the absence of cytosol-to-cytosol communication via astrocyte-oligodendrocyte gap junction channels. Indeed, by comparing the transcriptomes of immortalized precursor oligodendrocyte (Oli-neu) cells when cultured alone and cocultured with non-touching astrocytes we found profound changes in gene expression level, control and networking. Remarkably, the astrocyte proximity was more effective in remodeling the myelination (MYE) gene fabric and its control by cytokine receptor (CYR) modulated intercellular Ca2+-signaling (ICS) transcriptomic network than the db-cAMP treatment induced transformation into myelin-associated glycoprotein-positive oligodendrocyte-like cells. Moreover, astrocyte proximity up-regulated 37 MYE genes and switched on another 14 MYE, 23 ICS and 4 CYR genes, enhancing the roles of the leukemia inhibitory factor receptor and connexins Cx29 and Cx47. The novel Prominent Gene Analysis identified enhancer of zeste homolog 2 as the most relevant MYE gene in the astrocyte proximity, notch gene homolog1 in control and B-cell leukemia/lymphoma 2 in differentiated Oli-neu cells.

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Altered expression of signaling pathways regulating neuronal excitability in hippocampal tissue of temporal lobe epilepsy patients with low and high seizure frequency

Project description:Despite recent advances in our understanding of synaptic transmission associated with epileptogenesis, the molecular mechanisms that control seizure frequency in patients with temporal lobe epilepsy (TLE) remain obscure. RNA-Seq was performed on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. Differential expression (DE) analysis of individuals with low (LSF, mean= 4 seizure/month) versus high (HSF, mean= 60 seizures/month) seizure frequency identified 979 genes with ≥2-fold change in transcript abundance (FDR-adjusted p-value <0.05). Comparisons with post-mortem controls revealed a large number of downregulated genes in the HSF (1,676) versus LSF (399) groups. More than 50 signaling pathways were inferred to be deactivated or activated, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both groups, key neuronal system pathways were systematically deactivated in the HSF group, including calcium, CREB and Opioid signaling. We also infer that enhanced expression of a signaling cascade promoting synaptic downscaling may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE.

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Effect of WS974536 on astrocyte proteomics

Project description:Astrocyte-derived L-serine was found to regulate interstitial D-serine levels and seizure activity in a process controlled by phosphoserine phosphatase (PSPH). We identified a potent PSPH inhibitor, WS974536,nd found that its systemic administration dramatically reduced the frequency of spontaneous epileptic discharges in mouse and cynomolgus monkey models of TLE. In the project. We studied the effect of WS974536 on astrocytes by proteomics.

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FABP7 drives an inflammatory response in human astrocytes

Project description:FABP7 drives an inflammatory response in human astrocytes

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