Project description:Label-free proteomics of human brain FFPE archival tissue. Comparison of proteome composition between epilepsy and controls across 3 brain regions.
Project description:We utilize a rapid shotgun FFPE LFQ MS method to profile four regions of developing human cerebrum. Regions encompass neural precursor rich ventricular zones as well as intermediate and subplate and cortex regions accross human development from gestational weeks 16-36. Proteome signatures of the four fetal brain regions were determined using statistical tests and CMV-infected fetal brain encephalitis was analyzed to determine the region-specific effects of this neurodevelopmental disorder.
Project description:Brainstem nuclei dysfunction is implicated in sudden unexpected death in epilepsy (SUDEP). In animal models, deficient serotonergic activity is associated with seizure-induced respiratory arrest. In humans, glia are decreased in the ventrolateral medullary pre-Botzinger complex that modulates respiratory rhythm, as well as in the medial raphe that modulates respiration and arousal. Finally, SUDEP cases have decreased midbrain volume.
To understand the potential role of brainstem nuclei in SUDEP, we evaluated molecular signaling pathways using localized proteomics in microdissected midbrain dorsal raphe and medullary raphe serotonergic nuclei, as well as the ventrolateral medulla in brain tissue from epilepsy patients who died of SUDEP and other causes in diverse epilepsy syndromes, and non-epilepsy control cases
Project description:Epilepsy frequently develops as a result of brain insult, for example brain injury or stroke. Currently there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed miRNA levels in blood samples using Affymetrix microarrays 4.1 and performed comparative analysis of samples. We performed 3 comparisons: i) control animals vs. Status epilepticus animals, ii) animals which developed first spontaneous seizure around 7 days post stimulation (EARLY), or later after 21days post stimulation (LATE), iii) animals that had high or low number of seizures as determined by seizures number (EARLY vs. LATE).
Project description:Epilepsy frequently develops as a result of brain insult, for example brain injury or stroke. Currently there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed miRNA levels in blood samples using Affymetrix microarrays 4.1 and performed comparative analysis of samples. We performed 3 comparisons: i) control animals vs. Status epilepticus animals, ii) animals which developed first spontaneous seizure around 7 days post stimulation (EARLY), or later after 21days post stimulation (LATE), iii) animals that had high or low number of seizures as determined by seizures number (EARLY vs. LATE).
Project description:Epilepsy frequently develops as a result of brain insult, for example brain injury or stroke. Currently there are no tools allowing us to predict which trauma patients will eventually develop epilepsy. There is evidence that microRNAs levels are altered in the blood, making them attractive candidates for peripheral biomarkers of epilepsy. We analyzed miRNA levels in blood samples using Affymetrix microarrays 4.1 and performed comparative analysis of samples. We performed 3 comparisons: i) control animals vs. Status epilepticus animals, ii) animals which developed first spontaneous seizure around 7 days post stimulation (EARLY), or later after 21days post stimulation (LATE), iii) animals that had high or low number of seizures as determined by seizures number (EARLY vs. LATE).
Project description:Primary brain cancers are highly heterogeneous and include the most prevalent and aggressive glioblastomas. To understand the key factors underlying brain tumourigenesis, we have built our own database based on RNA sequencing from FFPE-derived biomaterial.
Project description:The diagnosis of epilepsy is complex and challenging and would benefit from the availability of molecular biomarkers, ideally measurable in a biofluid such as blood. Experimental and human epilepsy are associated with altered brain and blood levels of various microRNAs (miRNAs). Evidence is lacking, however, as to whether any of the circulating pool of miRNAs originates from the brain. To explore the link between circulating miRNAs and the pathophysiology of epilepsy, we first sequenced Ago2-bound miRNAs in plasma samples collected from mice subject to status epilepticus (SE) induced by intraamygdala microinjection of kainic acid. This identified time-dependent changes in plasma levels of miRNAs with known neuronal and microglial-cell origins. To explore whether the circulating miRNAs had originated from the brain, we generated mice expressing FLAG-Ago2 in neurons or microglia using tamoxifen-inducible Thy1 or Cx3cr1 promoters, respectively. FLAG immunoprecipitates from the plasma of these mice after seizures contained miRNAs, including let-7i-5p and miR-19b-3p. Taken together, these studies confirm that a portion of the circulating pool of miRNAs in experimental epilepsy originates from the brain, increasing support for miRNAs as mechanistic biomarkers of epilepsy.