10.3389/fncel.2018.00055.s003
Robin Cloarec
Robin
Cloarec
Sylvian Bauer
Sylvian
Bauer
Natacha Teissier
Natacha
Teissier
Fabienne Schaller
Fabienne
Schaller
Hervé Luche
Hervé
Luche
Sandra Courtens
Sandra
Courtens
Manal Salmi
Manal
Salmi
Vanessa Pauly
Vanessa
Pauly
Emilie Bois
Emilie
Bois
Emilie Pallesi-Pocachard
Emilie
Pallesi-Pocachard
Emmanuelle Buhler
Emmanuelle
Buhler
François J. Michel
François
J. Michel
Pierre Gressens
Pierre
Gressens
Marie Malissen
Marie
Malissen
Thomas Stamminger
Thomas
Stamminger
Daniel N. Streblow
Daniel
N. Streblow
Nadine Bruneau
Nadine
Bruneau
Pierre Szepetowski
Pierre
Szepetowski
Table2.XLSX
Frontiers
2018
cytomegalovirus
microglia
rat model
fetal brain
neurological outcome
2018-03-06 04:28:26
Dataset
https://frontiersin.figshare.com/articles/dataset/Table2_XLSX/5950813
<p>Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain.</p>