Abstract:
:Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral origin alter brain cell communication remain poorly understood. Here, we combined single-molecule tracking, calcium imaging, and behavioral approaches to demonstrate that the envelope protein (Env) of HERV type W, which is normally silenced but expressed in patients with neuropsychiatric conditions, alters the N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic organization and plasticity through glia- and cytokine-dependent changes. Env expression in the developing hippocampus was sufficient to induce behavioral impairments at the adult stage that were prevented by Env neutralization or tuning of NMDAR trafficking. Thus, we show that a HERV gene product alters glutamate synapse maturation and generates behavioral deficits, further supporting the possible etiological interplay between genetic, immune, and synaptic factors in psychosis.
journal_name
Sci Advjournal_title
Science advancesauthors
Johansson EM,Bouchet D,Tamouza R,Ellul P,Morr AS,Avignone E,Germi R,Leboyer M,Perron H,Groc Ldoi
10.1126/sciadv.abc0708subject
Has Abstractpub_date
2020-07-17 00:00:00pages
eabc0708issue
29issn
2375-2548pii
abc0708journal_volume
6pub_type
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