[en] Cognitive deficits, a characteristic feature of neuropsychiatric disorders, reflect perturbed activity in neuronal networks. Increasing evidence has linked neuroinflammation to impaired neuronal activity and resulting cognitive dysfunction, yet the underlying cellular mechanisms and developmental dynamics remain largely unclear. Here, we address this knowledge gap by investigating the Df(16)A mouse model of human 22q11.2 microdeletions, a prevalent chromosomal abnormality associated with an increased incidence of neuropsychiatric disorders. During early postnatal development, Df(16)A+/- mice show an imbalance of inflammatory signaling markers accompanied by increased microglial density in the superficial layers of the prefrontal cortex. Consequently, spine densities of pyramidal neurons were decreased, resulting in disrupted patterns of prefrontal neuronal activity during development and poor performance in a set-shifting task at juvenile age. Early treatment with minocycline, an anti-inflammatory drug, lastingly rescued these deficits in Df(16)A+/- mice, rebalancing signaling cascades and restoring neural activity as well as cognitive performance. These findings identify the early rebalancing of inflammatory signaling cascades as a promising therapeutic strategy for mitigating pathophysiological trajectories associated with the 22q11.2 deletion syndrome.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Günther, Anne ; Institute of Developmental Neurosciences, Center for Molecular Neurobiology, Hamburg Center of Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany. Electronic address: anne.guenther@zmnh.uni-hamburg.de
Chini, Mattia ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Bitzenhofer, Sebastian H; Institute of Developmental Neurosciences, Center for Molecular Neurobiology, Hamburg Center of Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany, Neural Circuit Physiology, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
Marquardt, Annette; Institute of Developmental Neurosciences, Center for Molecular Neurobiology, Hamburg Center of Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany
Hanganu-Opatz, Ileana L; Institute of Developmental Neurosciences, Center for Molecular Neurobiology, Hamburg Center of Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany. Electronic address: hangop@zmnh.uni-hamburg.de
Language :
English
Title :
Early rebalancing of neuroinflammatory cascades lastingly rescues prefrontal deficits in a 22q11.2ds model.
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