Johannes Steffen, Divija Deshpande, Henning Peter Düsedau, Janna Schmitz, Caio Andreeta Figueiredo, Laura Velleman, Claudia Pitzer, Christoph S N Klose, Ildiko R Dunay
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引用次数: 0
Abstract
The immune system provides multiple layers of protection that extend beyond conventional pathogen defense, including context-dependent modulation of behavior. However, the mechanisms driving these immune-mediated behavioral modifications remain incompletely understood. Here, we demonstrate that group 2 innate lymphoid cells (ILC2s) shape hippocampal synaptic development during early postnatal stages, with lasting effects on adult behavior, learning, and memory.Using flow synaptometry, we identified a selective reduction in hippocampal VGAT+ GABAergic/glycinergic inhibitory synapse frequency at postnatal day 15 in ILC2-deficient mice, while the proportions of inhibitory GABAergic (NL2+) or excitatory glutamatergic (GluR1+) synapses remained unaltered. These synaptic changes occurred without detectable phenotypical changes in cortical and hippocampal microglia. In adulthood, ILC2-deficient mice displayed significant impairments in hippocampus-dependent tasks, such as active place avoidance and operant conditioning, reflecting deficits in learning and memory.Our findings reveal a critical role for ILC2s in the formation of inhibitory synapses in the hippocampus, highlighting the impact of immune signaling on neuronal network maturation during a crucial period of brain development. This early immune-mediated modulation may have lasting effects on neuronal circuitry and cognitive functions that persist into adulthood, emphasizing the long-term implications of neuro-immune interactions for normal cognitive development and function.
期刊介绍:
The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes.
Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems.
The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.