Early Life Social Stress Causes Sex- and Region-Dependent Dopaminergic Changes that Are Prevented by Minocycline

Clarissa Catale, Luisa Lo Iacono, Alessandro Martini, Constantin Heil, Ezia Guatteo, Nicola Biagio Mercuri, Maria Teresa Viscomi, Daniela Palacios, Valeria Carola

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Early life stress (ELS) is known to modify trajectories of brain dopaminergic development, but the mechanisms underlying have not been determined. ELS perturbs immune system and microglia reactivity, and inflammation and microglia influence dopaminergic transmission and development. Whether microglia mediate the effects of ELS on dopamine (DA) system development is still unknown. We explored the effects of repeated early social stress on development of the dopaminergic system in male and female mice through histological, electrophysiological, and transcriptomic analyses. Furthermore, we tested whether these effects could be mediated by ELS-induced altered microglia/immune activity through a pharmacological approach. We found that social stress in early life altered DA neurons morphology, reduced dopamine transporter (DAT) and tyrosine hydroxylase expression, and lowered DAT-mediated currents in the ventral tegmental area but not substantia nigra of male mice only. Notably, stress-induced DA alterations were prevented by minocycline, an inhibitor of microglia activation. Transcriptome analysis in the developing male ventral tegmental area revealed that ELS caused downregulation of dopaminergic transmission and alteration in hormonal and peptide signaling pathways. Results from this study offer new insight into the mechanisms of stress response and altered brain dopaminergic maturation after ELS, providing evidence of neuroimmune interaction, sex differences, and regional specificity.
Lingua originaleEnglish
pagine (da-a)3913-3932
RivistaMolecular Neurobiology
Volume59
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Dopaminergic neurons
  • Early life stress
  • Microglia
  • RNA sequencing
  • Sex differences
  • Substantia nigra
  • Ventral tegmental area

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