Groundbreaking research emerging from the University of Cincinnati College of Medicine is shedding new light on the complex interplay between immune cells in the adult brain and the ongoing generation of neurons, a phenomenon known as adult neurogenesis. This novel insight challenges longstanding dogmas about brain plasticity and opens exciting avenues for understanding cognitive health and the aging process.
The research, published recently in the prestigious journal Nature Communications, addresses the intricate mechanisms by which microglia, the brain’s resident immune cells, modulate neurogenesis in the adult hippocampus. This brain region is critically involved in learning and memory formation, and the authors’ findings spotlight how immune surveillance and signaling by microglia can directly influence the creation and integration of new neurons into existing neural circuits.
Yu (Agnes) Luo, PhD, the study’s corresponding author and a professor and vice chair for research at the Department of Molecular and Cellular Biosciences, emphasizes the vital importance of understanding adult neurogenesis not only for our fundamental grasp of brain function but also for its implications in neurodegenerative diseases and mood disorders. “Adult neurogenesis is fundamental for maintaining cognitive flexibility, mood regulation, and memory consolidation,” Luo explains. “Elucidating the cellular crosstalk that facilitates this process could lead to breakthroughs in therapies aimed at combating cognitive decline and neurological diseases.”
The debate over adult neurogenesis has been contentious, with early skepticism regarding whether new neurons are generated in the adult human brain at all. It was not until a seminal 2025 study published in the journal Science that definitive evidence demonstrated ongoing neurogenesis within the hippocampus in adult humans. Building on this foundational knowledge, Luo’s laboratory sought to untangle the regulatory factors that enable or inhibit this process.
Central to their discoveries is the identification of microglia as dynamic regulators of neurogenesis. These cells, historically viewed largely as immune sentinels responding to injury or disease, are now recognized for their nuanced roles in maintaining neural homeostasis. The study reveals that the activation state of microglia critically determines their impact on neural stem cells — either promoting or suppressing the generation of newborn neurons depending on microglial signaling pathways.
One of the study’s most significant innovations lies in deciphering the role of transforming growth factor-beta (TGF-beta) signaling within microglia. Activated microglia devoid of TGF-beta signaling were found to foster neurogenesis via a sophisticated molecular conversation with neural stem cells. This bidirectional communication, described technically as microglia-neural stem cell signaling crosstalk, orchestrates the balance between immune function and neural regeneration, suggesting potential targets for rejuvenating the aging brain.
Though the current investigations were conducted in animal models to manipulate and observe cellular interactions within controlled environments, efforts are underway to translate these insights into human biology. Luo is collaborating with Ziyuan Guo, PhD, from the Department of Pediatrics at the College of Medicine, whose expertise lies in engineering human central nervous system organoids that integrate microglia, serving as sophisticated platforms for studying human neurodevelopment and neurodegeneration in vitro.
The project further benefited from cutting-edge single-cell RNA sequencing techniques, executed in partnership with Krishna Roskin, PhD, at Cincinnati Children’s Hospital. This technology allowed the team to map gene expression profiles at an unprecedented resolution, illuminating specific cellular signaling networks at work within the neurogenic niche. Such granular data deepens our understanding of the cellular diversity and molecular dialogues underpinning brain plasticity.
Longer-term, this research holds promise for revolutionary therapies aiming to harness adult neurogenesis for cognitive rejuvenation, particularly in the context of aging and Alzheimer’s disease. Joshua Peter, a lead author and former graduate student of the Luo lab, articulates this vision: “By understanding and potentially enhancing neurogenesis, we hope to mitigate cognitive decline and promote healthier brain aging, opening new therapeutic windows for Alzheimer’s and related disorders.”
The technology prowess gained through this research has also equipped emerging scientists like Peter and Kierra Ware, another Luo lab alumnus, with valuable expertise in translational neurobiology and biomedical research, ensuring a pipeline of innovators committed to pushing the frontiers of neuroscience.
Collaboration across institutions and disciplines bolsters the robustness of these findings. Contributors include Shane Liddelow from NYU Grossman School of Medicine, experts from the UChicago Medicine and NorthShore University HealthSystem partnership, as well as researchers from the German Center for Neurodegenerative Diseases. This international and interdisciplinary teamwork underscores the global effort to unveil the mysteries of the adult brain’s regenerative potential.
Taken together, these discoveries affirm the profound plasticity of the adult brain and redefine the roles of immune cells beyond mere defense—positioning them as key architects in neural regeneration. As research advances, the modulation of microglia signaling pathways stands as a promising frontier, potentially leading to innovative treatments that will transform the management of cognitive impairment and neurodegeneration.
Subject of Research: Animals
Article Title: Immune cells regulate adult hippocampal neurogenesis via TGF-beta signaling pathways
News Publication Date: 9-Feb-2026
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References: Nature Communications, 9-Feb-2026
Keywords: Adult neurogenesis, Hippocampal neurogenesis, Immune system, Microglia, TGF-beta signaling, Neural stem cells, Brain plasticity, Alzheimer’s disease, Cognition, Neurodegenerative diseases, Neurons, Brain development
Tags: adult neurogenesis researchbrain plasticity discoveriescellular crosstalk in the braincognitive health and aginghippocampus and memory formationimmune cells in the brainmechanisms of neuronal survivalmicroglia role in neurogenesismood disorders and neurogenesisNature Communications publicationneurodegenerative disease implicationsUniversity of Cincinnati neuroscience study
