Original Research ARTICLE
Neural damage in experimental Trypanosoma brucei gambiense infection: hypothalamic peptidergic sleep and wake-regulatory neurons
- 1Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Italy
- 2National Institute of Biomedical Research, Democratic Republic of Congo
- 3Istituto Nazionale di Neuroscienze (INN), Italy
Neuron populations of the lateral hypothalamus which synthesize the orexin (OX)/hypocretin or melanin-concentrating hormone (MCH) peptides play crucial, reciprocal roles in regulating wake stability and sleep. The disease human African trypanosomiasis (HAT), also called sleeping sickness, caused by extracellular Trypanosoma brucei (T. b.) parasites, leads to characteristic sleep-wake cycle disruption and narcoleptic-like alterations of the sleep structure. Previous studies have revealed damage of OX and MCH neurons during systemic infection of laboratory rodents with the non-human pathogenic T. b. brucei subspecies. No information is available, however, on these peptidergic neurons after systemic infection with T. b. gambiense, the etiological agent of 97% of HAT cases. The present study was aimed at the investigation of immunohistochemically characterized OX and MCH neurons after T. b. gambiense or T. b. brucei infection of a susceptible rodent, the multimammate mouse, Mastomys natalensis. Cell counts and evaluation of OX fiber density were performed at 4 and 8 weeks post-infection, when parasites had entered the brain parenchyma from the periphery. A significant decrease of OX neurons (about 44% reduction) and MCH neurons (about 54% reduction) was found in the lateral hypothalamus and perifornical area at 8 weeks in T. b. gambiense-infected M. natalensis. A moderate decrease (21% and 24% reduction, respectively), which did not reach statistical significance, was found after T. b. brucei infection. In two key targets of diencephalic orexinergic innervation, the peri-suprachiasmatic nucleus region and the thalamic paraventricular nucleus, densitometric analyses showed a significant progressive decrease in the density of orexinergic fibers in both infection paradigms, and especially during T. b. gambiense infection. Altogether the findings provide novel information showing that OX and MCH neurons are highly vulnerable to chronic neuroinflammatory signaling caused by the infection of human-pathogenic African trypanosomes.
Keywords: Human African Trypanosomiasis, orexin, hypocretin, melanin-concentrating hormone, Neuroinflammation, Sleep, wake
Received: 07 Dec 2017;
Accepted: 07 Feb 2018.
Edited by:Nouria Lakhdar-Ghazal, Faculty of science, Mohammed V university, Morocco
Reviewed by:Jackson C. Bittencourt, University of São Paulo, Brazil
Khalid El Allali, Hanna II Agronomy and veterinary institute, Morocco
Copyright: © 2018 Laperchia, Xu, Mumba Ngoy, Cotrufo and Bentivoglio. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MD. Marina Bentivoglio, University of Verona, Department of Neuroscience, Biomedicine and Movement Sciences, Verona, 37134, Italy, email@example.com