Ion channel candidates mediating orexin neuropeptide actions on brainstem serotonergic neurons
| العنوان: | Ion channel candidates mediating orexin neuropeptide actions on brainstem serotonergic neurons |
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| المؤلفون: | Javed, Saqlain |
| المصدر: | NYMC Student Theses and Dissertations |
| بيانات النشر: | Touro Scholar |
| سنة النشر: | 2021 |
| المجموعة: | Touro College & University System: Touro Scholar |
| مصطلحات موضوعية: | Orexin, Narcolepsy, Cataplexy, Serotonergic neurons, Nalcn, Dorsal Raphe, ion channel, neuropeptide, single cell RNA sequencing, Immunostaining, Medicine and Health Sciences, Nervous System, Nervous System Diseases |
| الوصف: | A loss of neurons that synthesize the neuropeptide orexin produces the sleep disorder narcolepsy with cataplexy in humans and other animals. How symptoms of this disorder arise is not well understood, but selectively restoring orexin actions at 5-HT DR neurons rescues key symptoms (cataplexy), suggesting normal orexin signaling is important at these neurons. To better understand how orexin acts on these neurons, our lab identified a set of novel orexin actions that appear mediated by unidentified cation- permeable ion channels. To narrow down the list of possible channels, we used a bioinformatics approach to compare published gene expression profiles of 5-HT neurons and cerebellar Purkinje neurons. These neurons, despite having different electrical properties and different orexin responses, have cation permeable ion channels. By using the Amigo2 database, we selected calcium channels, glutamate receptors, histamine receptors, inositol 1,4,5-triphosphate (IP3) receptors, ryanodine receptors, transient receptor potential (TRP) channels, potassium channels and sodium channels for examination. We then processed single-cell RNA sequencing (scRNAseq) data available on NCBI for 32 serotonergic neurons (SRP064626; from the Dymecki lab at Harvard) and 32 Purkinje cells (Series GSE78424). Single-cell RNA sequencing for both 5-HT neurons and Purkinje neurons were conducted using Illumina HiSeq 2500. After normalization of gene expression profiles of these 64 single cells and comparisons of gene expression levels between cell clusters and cell sub-clusters, we identified channels enriched in a subset of 5-HT neurons. Based on published channel properties and experimental data from our lab, we isolated 39 candidate channel genes, from which we selected the Nalcn gene for initial testing. Nalcn encodes a sodium leak and G protein-coupled receptor activated channel that regulates the resting membrane potential and neuronal excitability. It was up-regulated in 5-HT neurons compared to Purkinje cells (p = 1.6e-06) and it ... |
| نوع الوثيقة: | other/unknown material |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://touroscholar.touro.edu/nymc_students_theses/18Test; https://touroscholar.touro.edu/context/nymc_students_theses/article/1023/viewcontent/Saqlain__Javed_Master_s_Thesis_2021.pdfTest; https://touroscholar.touro.edu/context/nymc_students_theses/article/1023/filename/0/type/additional/viewcontent/Thesis_signature_page.pdfTest |
| الإتاحة: | https://touroscholar.touro.edu/nymc_students_theses/18Test https://touroscholar.touro.edu/context/nymc_students_theses/article/1023/viewcontent/Saqlain__Javed_Master_s_Thesis_2021.pdfTest https://touroscholar.touro.edu/context/nymc_students_theses/article/1023/filename/0/type/additional/viewcontent/Thesis_signature_page.pdfTest |
| رقم الانضمام: | edsbas.9F710FD8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |