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Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection

Flowerdew, SE and Wick, D and Himmelein, S and Horn, AKE and Sinicina, I and Strupp, M and Brandt, T and Theil, D and Hufner, K (2013) Characterization of neuronal populations in the human trigeminal ganglion and their association with latent herpes simplex virus-1 infection. PLoS One.

Abstract

Following primary infection Herpes simplex virus-1 (HSV-1) establishes lifelong latency in the neurons of human sensory ganglia. Upon reactivation HSV-1 can cause neurological diseases such as facial palsy, vestibular neuritis or encephalitis. Certain populations of sensory neurons have been shown to be more susceptible to latent infection in the animal model, but this has not been addressed in human tissue. In the present study, trigeminal ganglion (TG) neurons expressing six neuronal marker proteins were characterized, based on staining with antibodies against the GDNF family ligand receptor Ret, the high-affinity nerve growth factor receptor TrkA, neuronal nitric oxide synthase (nNOS), the antibody RT97 against 200kDa neurofilament, calcitonin gene-related peptide and peripherin. The frequencies of marker-positive neurons and their average neuronal sizes were assessed, with TrkA-positive (61.82%) neurons being the most abundant, and Ret-positive (26.93%) the least prevalent. Neurons positive with the antibody RT97 (1253 mm2 ) were the largest, and those stained against peripherin (884 mm2) were the smallest. Dual immunofluorescence revealed at least a 4.5% overlap for every tested marker combination, with overlap for the combinations TrkA/Ret, TrkA/RT97 and Ret/nNOS lower, and the overlap between Ret/CGRP being higher than would be expected by chance. With respect to latent HSV-1 infection, latency associated transcripts (LAT) were detected using in situ hybridization (ISH) in neurons expressing each of the marker proteins. In contrast to the mouse model, co-localization with neuronal markers Ret or CGRP mirrored the magnitude of these neuron populations, whereas for the other four neuronal markers fewer marker-positive cells were also LAT-ISH+. Ret and CGRP are both known to label neurons related to pain signaling. Copyright: 2013 Flowerdew et al

Item Type: Article
Additional Information: pubid: 46 nvp_institute: NIBR contributor_address: (Flowerdew, Wick, Himmelein, Strupp, Theil, Hufner) Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany (Flowerdew, Wick, Himmelein, Horn, Strupp, Brandt, Hufner) German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany (Horn) Institute of Anatomy, Department I, Ludwig-Maximilians University, Munich, Germany (Sinicina) Department of Legal Medicine, Ludwig-Maximilians University, Munich, Germany (Brandt) Institute for Clinical Neurosciences, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany (Theil) Preclinical Safety, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland (Hufner) Department of Biological Psychiatry, Medical University of Innsbruck, Innsbruck, Austria
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/21894

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