Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis.

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 Adv

journal_title

Science advances

authors

Johansson EM,Bouchet D,Tamouza R,Ellul P,Morr AS,Avignone E,Germi R,Leboyer M,Perron H,Groc L

doi

10.1126/sciadv.abc0708

subject

Has Abstract

pub_date

2020-07-17 00:00:00

pages

eabc0708

issue

29

issn

2375-2548

pii

abc0708

journal_volume

6

pub_type

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