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Social isolation leads to mild social recognition impairment and losses in brain cellularity

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Abstract

Chronic social stress is a significant risk factor for several neuropsychiatric disorders, mainly major depressive disorder (MDD). In this way, patients with clinical depression may display many symptoms, including disrupted social behavior and anxiety. However, like many other psychiatric diseases, MDD has a very complex etiology and pathophysiology. Because social isolation is one of the multiple depression-inducing factors in humans, this study aims to understand better the link between social stress and MDD using an animal model based on social isolation after weaning, which is known to produce social stress in mice. We focused on cellular composition and white matter integrity to establish possible links with the abnormal social behavior that rodents isolated after weaning displayed in the three-chamber social approach and recognition tests. We used the isotropic fractionator method to assess brain cellularity, which allows us to robustly estimate the number of oligodendrocytes and neurons in dissected brain regions. In addition, diffusion tensor imaging (DTI) was employed to analyze white matter microstructure. Results have shown that post-weaning social isolation impairs social recognition and reduces the number of neurons and oligodendrocytes in important brain regions involved in social behavior, such as the anterior neocortex and the olfactory bulb. Despite the limitations of animal models of psychological traits, evidence suggests that behavioral impairments observed in patients might have similar biological underpinnings.

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Adapted from Franklin and Paxinos 2001. B. Representative DTI image of the brain of one of the animals, at a similar plane as represented in A

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Raw data can be shared via a request to the corresponding authors.

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Acknowledgements

We want to thank Camila Madeira Lopes, Camila Gomes da Silva, Ludmila Ribeiro, Fernanda Meireles, and Caroline Victorino for technical support, and Lena Rubim Pereira for administrative assistance.

Funding

This study received funding from the Brazilian Council for Scientific and Technological Development (CNPq, grant # 470734/2012–4), and the Rio de Janeiro Foundation for the Support of Science (FAPERJ, grant # E-26/010.002983/2014), and the National Institute of Translational Neuroscience (grant # 465346/2014–6).

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Contributions

DMG, FTM, and RL designed the study. RL and FTM supervised the study. DMG, GAN, and BV-G collected the behavioral data, and DMG, BV-G, and RJV-B collected the MRI data. DMG, BV-G, and WO collected the cell counting data. DMG performed behavioral, MRI, and cell counting data analysis and wrote the manuscript. GAN performed behavioral data analysis. RL and FTM edited the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Daniel Menezes Guimarães or Roberto Lent.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

All procedures followed the terms of the Ethics Committee on the Use of Animals (CEUA) of the Federal University of Rio de Janeiro (Protocol# 01200.001568/2013–87).

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Guimarães, D.M., Valério-Gomes, B., Vianna-Barbosa, R.J. et al. Social isolation leads to mild social recognition impairment and losses in brain cellularity. Brain Struct Funct 228, 2051–2066 (2023). https://doi.org/10.1007/s00429-023-02705-z

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  • DOI: https://doi.org/10.1007/s00429-023-02705-z

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