EARLY MATERNAL DEPRIVATION MODULATES DISTRIBUTION OF INTERLEUKIN-1 AND NMDA RECEPTORS AT THE SYNAPTIC MEMBRANE

Severe stress early in life induces changes in neuronal function, determining a different setting in synaptic organization, which could be implicated in promoting an adaptive response under physiological conditions and/or in stress-related disorders later in life. The pro-inflammatory citokine Interleukin-1β (IL-1β) has been recognised as a central regulator of stress responses. IL-1β signal transduction in neurons occurs through the IL-1 receptor type I (IL-1-RI). We recently demonstrated in primary hippocampal neurons that IL-1RI is enriched at synaptic sites, where it co-localizes with, and binds to the GluN2B subunit of NMDA receptor (NMDAR) suggesting a functional interaction. In a model of maternal deprivation (MD) we investigated the expression and distribution at the post-synaptic site of IL-1RI, together with the GluN2A and GluN2B subunits of the NMDAR and the GluR1 and GluR2 subunits of the AMPA receptors, in the hippocampus and pre-frontal cortex of male and female rats. 24h of MD at PND9 significantly increases the levels of IL-1RI, as well as IL-1RI interaction with GluN2B, at the synapsis of hippocampal neurons at PND 45. This effect is sex-dependent, occurring only in male rats. No such alterations were observed in the prefrontal cortex as well as no enrichment of GluN2B and GluN2A at the synapse is evident in PND 45 MD rats. On the contrary, both GluR1 and GluR2 subunits of the AMPAR at the hippocampal synapse were reduced in 45 PND MD rats. The decrease of AMPAR subunits at the post-synapses of male MD rats was coupled to a decreased phosphorylation at Tyr-1472 of the GluN2B subunit of the NMDAR. These data reveal a profound modification in the receptors organization at the post-synapses induced by MD in male rats hippocampi, suggesting the setting for an immature synapse which possibly affect neuronal sensitivity to both IL-1b and the glutamatergic neurotransmission.