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Cited by 26Neuroinflammation and Neurodegeneration MechanismsStress Responses and CortisolTryptophan and brain disorders

Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model

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Maras, Pamela M., Hebda-Bauer, Elaine K., Hagenauer, Megan H., Hilde, Kathryn L., Blandino, Peter, Watson, Stanley J., Akil, Huda·2022·Translational Psychiatry
DOI 10.1038/s41398-022-01821-4PMC PMC8924221

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Abstract

Microglia play critical roles in healthy brain development and function, as well as the neuropathology underlying a range of brain diseases. Despite evidence for a role of microglia in affective regulation and mood disorders, little is known regarding how variation in microglia status relates to individual differences in emotionality. Using a selective breeding model, we have generated rat lines with unique temperamental phenotypes that reflect broad emotional traits: bred low responder rats (bLRs) are novelty-averse and model a passive coping style, whereas bred high responder rats (bHRs) are highly exploratory and model an active coping style. To identify a functional role of microglia in these phenotypes, we administered minocycline, an antibiotic with potent microglia inhibiting properties and observed shifts in forced swim, sucrose preference, and social interaction behaviors in bLRs. Using detailed anatomical analyses, we compared hippocampal microglia profiles of bHRs and bLRs and found that although the lines had similar numbers of microglia, selective breeding was associated with a shift in the morphological features of these cells. Specifically, microglia from bLRs were characterized by a hyper-ramified morphology, with longer processes and more complicated branching patterns than microglia from bHRs. This morphology is thought to reflect an early stage of microglia activation and suggests that bLR microglia are in a reactive state even when animals are not overtly challenged. Taken together, our results provide novel evidence linking variation in inborn temperament with differences in the baseline status of microglia and implicate a role for microglia in shaping enduring emotional characteristics.

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Cited by

Sorted by citations

Authors
Maras, P. M., Hebda-Bauer, E. K., Hagenauer, M. H., Hilde, K. L., Blandino, P., Watson, S. J., & Akil, H.
Affiliations
University of Michigan (US)
Corresponding author
Maras, Pamela M.
ORCID
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2022-03-15
Volume
12
Issue
1
Pages
105-105
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/s41398-022-01821-4
PMC
PMC8924221
OpenAlex
W4220678673
Cited by
26
References
13
Citations by year
2026: 3 · 2025: 10 · 2024: 6 · 2023: 4 · 2022: 3
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • The Pritzker Neuropsychiatric Disorders Research Consortium
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01MH104261)
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (U01DA043098)
  • United States Department of Defense | United States Navy | Office of Naval Research (N00014-12-1-0366, N00014-19-1-2149)
  • The Pritzker Neuropsychiatric Research Consortium The Hope for Depression Research Foundation
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
microglia, microglial morphology, emotional temperament, selective breeding, minocycline, hippocampus, microglial activation, passive coping, active coping, exploratory behavior, emotion regulation
MeSH terms
Selective Breeding, Animals, Emotions, Problem Solving, Temperament, Microglia, Rats

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