Interactions between the nervous, immune, and endocrine systems in brain health

Brain health is the result of intricate communication between the nervous, immune, and endocrine systems. Traditionally, these systems were studied in isolation; however, recent advances highlight their dynamic crosstalk and their collective influence on brain function. Neuroinflammation, hormonal signaling, and immune responses are now recognized as critical factors in neurological development, homeostasis, and disease. Disruptions in these inter-system interactions are implicated in a myriad of conditions, such as neurodegenerative diseases, psychiatric disorders, and metabolic syndromes. As our understanding deepens, there is a growing appreciation for integrative approaches that examine these systems together, offering novel insights into mechanisms underlying brain health and disease.

This Research Topic aims to address the current gaps in understanding how the nervous, immune, and endocrine systems interact to regulate brain health across the lifespan. Despite emerging evidence that these systems communicate bidirectionally through signaling molecules, immune cells, and hormones, the precise mechanisms and their implications remain insufficiently explored. We seek to foster a comprehensive discussion that highlights both basic and translational research, uniting perspectives from neurobiology, immunology, and endocrinology. By doing so, we hope to identify new biomarkers, therapeutic targets, and prevention strategies for brain diseases. Ultimately, our goal is to accelerate multidisciplinary research that can unveil how these systems collectively contribute to brain resilience, aging, and vulnerability to disorders.
We welcome research focused on the interplay between the nervous, immune, and endocrine systems, while also encouraging contributions that address inflammation, the neuroimmune system, and neuroadaptations even in the absence of endocrine components. Submissions may include mechanistic studies, clinical research, or translational approaches, spanning both health and disease. We are particularly interested in work that explores how these systems interact to maintain homeostasis, how disruptions contribute to pathology, and how such insights may guide prevention or treatment strategies.

Authors are invited to address, but are not limited to, the following themes and guiding questions:

• Molecular and cellular mechanisms underlying neuro-immune-endocrine interactions: How do glial cells, cytokines, and neuropeptides coordinate signaling across these systems? What novel cellular mediators or feedback loops remain to be identified?
• Impact of inflammation and immune signaling on neuroendocrine regulation: How does chronic versus acute inflammation alter hypothalamic-pituitary-adrenal (HPA) axis function? In what ways do peripheral immune challenges reshape central stress responses?
• Role of hormones in mediating brain-immune communication: How do sex hormones modulate vulnerability or resilience to neurological disease? What roles do metabolic hormones (e.g., insulin, leptin) play in shaping immune responses within the brain?
• Influence of neuro-immune-endocrine crosstalk on aging, cognition, and neurodegenerative diseases: How do age-related changes in immune and endocrine function contribute to cognitive decline? Can interventions targeting these interactions slow or reverse neurodegeneration?
• Biomarkers and therapeutic approaches targeting system interactions for promoting brain health: What circulating or imaging biomarkers best capture inter-system dysregulation? How can multi-target therapies be developed to modulate cross-system pathways effectively?
• Effects of stress, infection, or metabolic status on inter-system dynamics: How do psychosocial stressors reshape immune and endocrine signaling in the brain? What role do infections or systemic metabolic imbalances play in precipitating or exacerbating brain disorders?

By framing these questions, we encourage contributions that span mechanistic studies, longitudinal human research, and translational interventions. We particularly welcome interdisciplinary collaborations that integrate molecular biology, clinical neuroscience, and systems-level approaches to better understand how nervous, immune, and endocrine interactions shape brain health across development, adulthood, and aging.