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Are microglia in charge of controlling stress-response behavior?

Molecular Psychiatry (2024)Cite this article

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Chronic anxiety is a widespread mental health challenge that affects a considerable population worldwide [1]. From 2008 to 2018, anxiety significantly risen in the United States, especially in young adults aged 18–25. This particular age group has experienced the most significant increase, which was faster than other age groups [1]. Anxiety significantly impacts patients’ daily functioning, psychological morbidity, and quality of life [2]. This condition is often present in neuropsychiatric disorders and is linked to stress-related behaviors [3]. Related to that, chronic stress exposure is linked to various neuropsychiatric illnesses, with stress correlating with dendritic hypertrophy and synaptic remodeling in the amygdala. These changes are circuit-specific and contribute to understanding the pathophysiological basis of depression, anxiety disorders, and other stress-related conditions [4]. However, our understanding of the molecular genetics behind chronic anxiety and its relation to stress is still limited. We have not yet made significant progress in explaining how an initial protective response mechanism can become detrimental over time.

A growing body of research indicates that a targeted disruption/mutation of the Hoxb8 gene or ablation of a microglial subpopulation induced chronic anxiety and OCSD-like behavior, compulsive pathological hair pulling, to the point of showing lesions at the sites of overgrooming [5, 6]. Hoxb8 is a transcription factor that controls development as part of the Homeobox gene family [7]. Moreover, Hoxb8 is responsible for the maintenance and differentiation of myeloid progenitor cells, which are one of the two sources of microglia. Chen et al. [8] found that the only detectable Hoxb8 labeled cell lineage in the brain (the source of the complex, innate behavioral grooming syntax) is microglia, supporting the hypothesis that the excessive pathological grooming behavior observed in Hoxb8 mutant mice originates from defective microglia, thus directly connecting hematopoietic function to mouse behavior. In the course of characterizing pathological and chronic anxiety, grooming behavior, and the role played by Hoxb8 microglia in this pathological manifestation, Nagarajan and Capecchi developed a mouse model using a method that earned Capecchi a Nobel Prize in 2007 [9].

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References

  1. Goodwin RD, Weinberger AH, Kim JH, Wu M, Galea S. Trends in anxiety among adults in the United States, 2008-2018: Rapid increases among young adults. J Psychiatr Res. 2020;130:441–6.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wilmer MT, Anderson K, Reynolds M. Correlates of Quality of Life in Anxiety Disorders: Review of Recent Research. Curr Psychiatry Rep. 2021;23:77.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res. 2012;21:169–84.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang JY, Liu TH, He Y, Pan HQ, Zhang WH, Yin XP, et al. Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner. Biol Psychiatry. 2019;85:189–201.

    Article  CAS  PubMed  Google Scholar 

  5. Nagarajan N, Jones BW, West PJ, Marc RE, Capecchi MR. Corticostriatal circuit defects in Hoxb8 mutant mice. Mol Psychiatry. 2018;23:1868–77.

    Article  CAS  PubMed  Google Scholar 

  6. Greer JM, Capecchi MR. Hoxb8 is required for normal grooming behavior in mice. Neuron. 2002;33:23–34.

    Article  CAS  PubMed  Google Scholar 

  7. Capecchi MR. Hox genes and mammalian development. Cold Spring Harb Symp Quant Biol. 1997;62:273–81.

    Article  CAS  PubMed  Google Scholar 

  8. Chen SK, Tvrdik P, Peden E, Cho S, Wu S, Spangrude G, et al. Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010;141:775–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nagarajan N, Capecchi MR. Optogenetic stimulation of mouse Hoxb8 microglia in specific regions of the brain induces anxiety, grooming, or both. Mol Psychiatry. 2023. Epub ahead of print.

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Funding

Funding

The research funding support from the University of Texas Health Science Center at Houston, the Louis A. Faillace, MD Endowment Funds, and the Translational Psychiatry Program to GS and JQ are acknowledged. The Translational Psychiatry Program (USA) is funded by a grant from the National Institute of Health/National Institute of Mental Health (1R21MH117636–01A1, to JQ), the Department of Psychiatry and Behavioral Sciences, McGovern Medical School at UTHealth, and Linda Gail Behavioral Health Research Fund. Center of Excellence on Mood Disorders (USA) is funded by the Pat Rutherford Jr Chair in Psychiatry, the John S. Dunn Foundation, and the Anne and Don Fizer Foundation Endowment for Depression Research. Translational Psychiatry Laboratory (Brazil) is funded by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Instituto Cérebro e Mente and University of Southern Santa Catarina (UNESC).

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Authors and Affiliations

  1. Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Rafaela C. Cordeiro, Giselli Scaini & João Quevedo

  2. Center for Interventional Psychiatry, Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Giselli Scaini & João Quevedo

  3. Center of Excellence on Mood Disorders, Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Giselli Scaini & João Quevedo

  4. Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA

    Giselli Scaini

  5. Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil

    João Quevedo

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  1. Rafaela C. Cordeiro
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  2. Giselli Scaini
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RCC and GS drafted the first version of this article, which was critically revised by JQ. In total, both authors contributed equally to this work.

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Correspondence to Giselli Scaini.

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Cordeiro, R.C., Scaini, G. & Quevedo, J. Are microglia in charge of controlling stress-response behavior?. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02511-x

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