2. Academic Validation
  3. Mast cells proliferate in the peri-hippocampal space during early development and modulate local and peripheral immune cells

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

  • Dev Cell. 2025 Mar 24;60(6):853-870.e7. doi: 10.1016/j.devcel.2024.11.015.
Alexa C Blanchard 1,  Anna Maximova 2,  Taylor Phillips-Jones 3,  Matthew R Bruce 3,  Pavlos Anastasiadis 4,  Christie V Dionisos 5,  Kaliroi Engel 5,  Erin Reinl 3,  Aidan Pham 5,  Sonia Malaiya 5,  Nevil Singh 6,  Seth Ament 7,  Margaret M McCarthy 8
Affiliations

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.

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