Cancer activates microglia to the same extent as chronic stress throughout stress neurocircuitry in a mouse model of breast cancer

Delyse McCaffrey; Adam J Lawther; Cynthia Shannon Weickert; Adam K Walker

doi:10.1016/j.psyneuen.2022.105938

Cancer activates microglia to the same extent as chronic stress throughout stress neurocircuitry in a mouse model of breast cancer

Psychoneuroendocrinology. 2022 Dec:146:105938. doi: 10.1016/j.psyneuen.2022.105938. Epub 2022 Sep 21.

Authors

Delyse McCaffrey¹, Adam J Lawther², Cynthia Shannon Weickert³, Adam K Walker⁴

Affiliations

¹ Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, New South Wales, Australia; Discipline of Psychiatry and Mental Health, Faculty of Medicine, University of New South Wales, Sydney, Australia.
² Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, New South Wales, Australia.
³ Discipline of Psychiatry and Mental Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, New South Wales, Australia; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY, USA.
⁴ Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, New South Wales, Australia; Discipline of Psychiatry and Mental Health, Faculty of Medicine, University of New South Wales, Sydney, Australia; Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Australia. Electronic address: a.walker@neura.edu.au.

PMID: 36174451
DOI: 10.1016/j.psyneuen.2022.105938

Abstract

The prevalence of stress-related comorbidities is increased approximately 3-fold in cancer patients compared to the general population. There is a scarcity of research focusing on the biological brain changes caused by the cancer due to the assumption that psychological symptoms are solely caused by the stress of a cancer diagnosis. Recent clinical evidence indicates that declines in cognition and increases in mood symptoms occur prior to an individual receiving a cancer diagnosis, suggesting that the cancer itself may play a role in mediating biological brain change. Furthermore, the presence of a tumour may change the brain response to environmental stressors unrelated to a cancer diagnosis. Using a syngeneic, orthotopic mouse model of breast cancer, we compared the impact of mammary tumours and chronic restraint stress on microglial and astrocytic activation throughout stress-relevant neurocircuitry. We also examined whether changes in microglial and astrocytic activation overlapped with changes in chronic neuronal activity. We show that cancer and chronic restraint stress activates microglia to the same magnitude in the same subcortical brain regions, and that this activation correlates with stress coping behaviours. The findings suggest that in some cancer patients, microglia may be activated in brain regions involved in interpreting and responding to psychological distress before they are aware of their diagnosis. In contrast, cancer reduced astrocyte reactivity in two cortical brain regions where there were no clear changes in response to chronic restraint stress. Taken together, it is likely that interventions that aim to improve anxiety and stress in cancer patients by targeting glial responses to cancer would need to be cell-specific; reducing microglial activation and/or stimulating astrocytic activation.

Keywords: Anxiety; Astrocytes; Breast cancer; Microglia; Neuroinflammation; Stress.