Biology subjects

Nemutlu, E.

Publications and source records attributed to Nemutlu, E..

3 recordsLinked to original sources

bioRxiv2024

Pathogenic microbiota disrupts the intact structure of cerebral organoids by altering energy metabolism

This study investigated the impact of different bacterial populations on the biomolecular structures of cerebral organoids (COs) at various levels. COs were co-cultured with non-pathogenic (NM) and pathogenic (PM) bacterial populations. PM reduced the number of TUJ1+ neurons and disrupted the intact structure of COs. In addition, PM was found to induce changes in the transcript profile of COs, including a decrease in the activity of the glycolysis pathway and an increase in the pentose phosphate pathway, leading to deterioration in cellular energy metabolism, which is linked to neurodegenerative diseases. Proteomic analysis revealed a unique cluster of proteins in COs. PM exposure upregulated proteins related to neurological diseases, consistent with RNA-seq data. Communication between bacteria and neural cells was demonstrated using 18O-stable isotope labeling (SIL)-based metabolic flux analysis. COs showed higher 18O-enrichment of TCA cycle intermediates when co-cultured with NM and PM, indicating increased oxidative phosphorylation activity upon exposure to bacteria. This study provides a useful platform to monitor metabolic signals and communication between microbiotas and human brain cells. The findings suggest that pathogenic bacteria release metabolites that alter biomolecular structures in brain organoids, potentially contributing to neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Metabolomic analysis of the effect of endocannabinoid metabolism inhibition in ovalbumin-induced allergic airway inflammation in Guinea pigs

Background and aimsAsthma manifests as a multifaceted airway inflammation. The therapeutic potential of targeting endocannabinoids in mitigating asthma remains incompletely elucidated. Therefore, we aim to scrutinize metabolic alterations, deepen our comprehension of the endocannabinoids therapeutic role, and discern novel biomarkers for monitoring allergic airway inflammation. MethodsGuinea pigs were sensitized with ovalbumin (150g) or PBS on days 1, 4, and 7. On day 14, they were exposed to aerosols containing 0.3% ovalbumin or PBS. Treatment groups were administered inhibitors of fatty acid amide hydrolase (FAAH) and/or monoacylglycerol lipase (MAGL) one hour prior to aerosol exposure. Subsequently, bronchoalveolar lavage (BAL), blood, and lung samples were collected on the following day for analysis using GC-MS. Metabolites were meticulously categorized into 10 distinct classifications based on their chemical and biological functions. Subsequently, they were further organized into 5 principal metabolic pathways for a comprehensive metabolomic analysis. ResultsOvalbumin exposure exclusively altered the metabolic profile in the lung. Conversely, inhibition of endocannabinoids metabolism induced a systemic shift in energy metabolites such as carbohydrates, amino and fatty acids. ConclusionsAllergen exposure induced an elevation in metabolites associated with glycolytic metabolism particularly in the lungs, indicating enhanced activation and increased numbers of immune cells. Notably, inhibition of endocannabinoids mitigated these shifts, underscoring its anti-inflammatory efficacy.

pharmacology and toxicology↗

bioRxiv2020

Partial inhibition of mitochondrial complex I attenuates neurodegeneration and restores energy homeostasis and synaptic function in a symptomatic Alzheimers mouse model

We demonstrate that mitochondrial respiratory chain complex I is an important small molecule druggable target in Alzheimers Disease (AD). Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 mice, a translational model of AD. Treatment of APP/PS1 mice with complex I inhibitor after the onset of AD-like neuropathology improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine maturation, cognitive function and proteostasis, and reduced oxidative stress and inflammation in brain and periphery, ultimately blocking the ongoing neurodegeneration. Therapeutic efficacy in vivo was monitored using translational biomarkers FDG-PET, 31P NMR, and metabolomics. Cross-validation of the mouse and the human AMP-AD transcriptomic data demonstrated that pathways improved by the treatment in APP/PS1 mice, including the immune system response and neurotransmission, represent mechanisms essential for therapeutic efficacy in AD patients.

neuroscience↗