Distribution of glutamate receptor, ionotropic, kainate 1 and neuropeptide calcitonin gene-related peptide mRNAs during formation of the embryonic and postnatal mouse molar in the maxilla
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER
Authors: Sunohara, Masataka; Kamata, Hiroaki; Maeda, Yuuki; Miwa, Yoko; Karibe, Hiroyuki; Sato, Iwao
The neuropeptide calcitonin gene-related peptide (CGRP) is a well-characterized neurotransmitter. Glutamate receptor, ionotropic, kainate 1 (Grik1) has also been demonstrated to generate high-affinity kainate receptors. However, little is known about the roles of CGRP and Grik1 during the developmental formation of teeth. In this study, we endeavoured to analyse the expression and localization of CGRP and Grik1 mRNAs using in situ hybridization on the mouse maxilla during development from the embryonic stage (E18.5) to after birth (P10, P15 and P20). We found that hybridization with an anti-sense probe for CGRP clearly localized in the maxilla at E18.5 in contrast to that of P15 and P20. Hybridization with an anti-sense probe for CGRP was not detected in the dental pulp of molars in the maxilla at P10, which is in contrast to Grik1 mRNA at the same developmental stage. Hybridization with an anti-sense probe for Grik1 mRNA was detected in the basal region of the dental pulp of molars at P10 and P15. Finally, these markers were not detected in molars in the mouse maxilla at P20. The ratio of positive cells for the hybridization signals of Grik1 and CGRP in the dental pulp decreased from E18.5 (p < 0.001). These features in CGRP and Grik1r mRNAs may indicate roles of function during tooth development between embryonic and postnatal stages with root formation and erupted movements. (C) 2019 Elsevier GmbH. All rights reserved.
Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP)
NPJ GENOMIC MEDICINE
Authors: Friedman, Daniel; Kannan, Kasthuri; Faustin, Arline; Shroff, Seema; Thomas, Cheddhi; Heguy, Adriana; Serrano, Jonathan; Snuderl, Matija; Devinsky, Orrin
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic-clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection. We compared identified variants from both groups filtering known polymorphisms from publicly available data as well as scanned for epilepsy and candidate SUDEP genes. In the SUDEP cohort, we identified mutually exclusive variants in genes involved in mu-opiod signaling, gamma-aminobutyric acid (GABA) and glutamate-mediated synaptic signaling, including ARRB2, ITPR1, GABRR2, SSTR5, GRIK1, CTNAP2, GRM8, GNAI2 and GRIK5. In SUDEP patients we also identified variants in genes associated with cardiac arrhythmia, including KCNMB1, KCNIP1, DPP6, JUP, F2, and TUBA3D, which were not present in living epilepsy controls. Our data shows that genomic analysis of brain tissue resected for seizure control can identify potential genetic biomarkers of SUDEP risk.