Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells

Alexa C Blanchard; Anna Maximova; Taylor Phillips-Jones; Matthew R Bruce; Pavlos Anastasiadis; Christie V Dionisos; Kaliroi Engel; Erin Reinl; Aidan Pham; Sonia Malaiya; Nevil Singh; Seth Ament; Margaret M McCarthy

doi:10.1016/j.devcel.2024.11.015

Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells

Dev Cell. 2024 Nov 30:S1534-5807(24)00697-X. doi: 10.1016/j.devcel.2024.11.015. Online ahead of print.

Authors

Affiliations

¹ Program in Molecular Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, MD, USA.
² Medical Scientist Training Program, University of Maryland School of Medicine, Baltimore, MD, USA; Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴ Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Medicine Institute for Neuroscience Discovery, University of Maryland, Baltimore, MD 21201, USA.
⁵ Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA.
⁶ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.
⁷ Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; Medicine Institute for Neuroscience Discovery, University of Maryland, Baltimore, MD 21201, USA.
⁸ Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA; University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA; Medicine Institute for Neuroscience Discovery, University of Maryland, Baltimore, MD 21201, USA. Electronic address: mmccarthy@som.umaryland.edu.

PMID: 39662467
DOI: 10.1016/j.devcel.2024.11.015

Abstract

Brain development is a non-linear process of regionally specific epochs occurring during windows of sensitivity to endogenous and exogenous stimuli. We have identified an epoch in the neonatal rat brain defined by a transient population of peri-hippocampal mast cells (phMCs) that are abundant from birth through 2-weeks post-natal but absent thereafter. The phMCs are maintained by proliferation and harbor a unique transcriptome compared with mast cells residing in the skin, bone marrow, or other brain regions. Pharmacological activation of this population broadly increases blood-brain barrier permeability, recruits peripheral immune cells, and stunts local microglia proliferation. Examination of the post-mortem human brain demonstrated mast cells in the peri-hippocampal region of a newborn, but not an older infant, suggesting a similar developmental period exists in humans. Mast cells specifically, and early-life inflammation generally, have been linked to heightened risk for neurodevelopmental disorders, and these results demonstrate a plausible source of that risk.

Keywords: CCL2; blood-brain-barrier; hippocampal development; hippocampus; inflammation; mast cells; microglia; monocytes; neurodevelopment; proliferation.