Citation

Théberge S, Belliveau C, Xie D, Khalaf R, Perlman K, Rahimian R, Davoli MA, Turecki G, Mechawar N. Cereb. Cortex 2024; 34(5): bhae197.

Copyright

(Copyright © 2024, Oxford University Press)

DOI

10.1093/cercor/bhae197

PMID

38760318

Abstract

Cortical parvalbumin interneurons (PV+) are major regulators of excitatory/inhibitory information processing, and their maturation is associated with the opening of developmental critical periods (CP). Recent studies reveal that cortical PV+ axons are myelinated, and that myelination along with perineuronal net (PNN) maturation around PV+ cells is associated with the closures of CP. Although PV+ interneurons are susceptible to early-life stress, their relationship between their myelination and PNN coverage remains unexplored. This study compared the fine features of PV+ interneurons in well-characterized human post-mortem ventromedial prefrontal cortex samples (n = 31) from depressed suicides with or without a history of child abuse (CA) and matched controls. In healthy controls, 81% of all sampled PV+ interneurons displayed a myelinated axon, while a subset (66%) of these cells also displayed a PNN, proposing a relationship between both attributes. Intriguingly, a 3-fold increase in the proportion of unmyelinated PV+ interneurons with a PNN was observed in CA victims, along with greater PV-immunofluorescence intensity in myelinated PV+ cells with a PNN. This study, which is the first to provide normative data on myelination and PNNs around PV+ interneurons in human neocortex, sheds further light on the cellular and molecular consequences of early-life adversity on cortical PV+ interneurons.

Language: en

Keywords

*Interneurons/pathology/metabolism; *Parvalbumins/metabolism; *Prefrontal Cortex/pathology/metabolism; Adult; Aged; Autopsy; child abuse; Child Abuse/psychology; Female; Humans; Male; Middle Aged; myelin; Myelin Sheath/pathology/metabolism; parvalbumin; perineuronal nets; post-mortem ventromedial prefrontal cortex; Suicide; Young Adult