Early maternal deprivation immunologically primes hippocampal synapses by redistributing interleukin-1 receptor type I in a sex dependent manner.
Challenges experienced in early life cause an enduring phenotypical shift of immune cells towards a sensitised state that may lead to an exacerbated reaction later in life and contribute to increased vulnerability to neurological diseases. Peripheral and central inflammation may affect neuronal function through cytokines such as IL-1. The extent to which an early life challenge induces long-term alteration of immune receptors organization in neurons has not been shown. We investigated whether a single episode of maternal deprivation (MD) on post-natal day (PND) 9 affects: (i) the synapse distribution of IL-1RI together with subunits of NMDA and AMPA receptors; and (ii) the interactions between IL-1RI and the GluN2B subunit of the NMDAR in the long-term, at PND 45. MD increased IL-1RI levels and IL-1RI interactions with GluN2B at the synapse of male hippocampal neurons, without affecting the total number of IL-1RI or NMDAR subunits. Although GluN2B and GluN2A were slightly but not significantly changed at the synapse, their ratio was significantly decreased in the hippocampus of the male rats who had experienced MD; the levels of the GluA1 and GluA2 subunits of the AMPAR were also decreased. These changes were not observed immediately after the MD episode. None of the observed alterations occurred in the hippocampus of the females or in the prefrontal cortex of either sex. These data reveal a long-term, sex-dependent modification in receptor organisation at the hippocampal post-synapses following MD. We suggest that this effect might contribute to priming hippocampal synapses to the action of IL-1β.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy. Electronic address: barbara.viviani@unimi.it.
Barbara
B
Viviani
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Mariaserena
M
Boraso
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
Manuel
M
Valero
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Fabrizio
F
Gardoni
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Eva Maria
EM
Marco
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain.
Ricardo
R
Llorente
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Emanuela
E
Corsini
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Corrado Lodovico
CL
Galli
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Monica
M
Di Luca
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Marina
M
Marinovich
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain; Departamento de Fisiología Humana, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
Meritxell
M
López-Gallardo
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Electronic address: pazviver@bio.ucm.es.
Maria-Paz
MP
Viveros
D000818:Animals; D015153:Blotting, Western; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000032:analysis; D008297:Male; D008426:Maternal Deprivation; D051381:Rats; D017208:Rats, Wistar; D053573:Receptors, Interleukin-1 Type I / Q000502:physiology*; D012737:Sex Factors; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000276:immunology* / Q000502:physiology
D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I
GluN2B; Immune priming; Interleukin receptor type I; Maternal deprivation; NMDA glutamate receptors; Sex differences