Abstract
Background : IQSEC2-related disorders are a genetic syndrome characterized by intellectual disability and various neurodevelopmental disorders. We previously generated Iqsec2 knockout mice and conducted electrophysiological and behavioral assays to study their phenotypic manifestations. However, histological features observed in other mouse models of neurodevelopmental disorders have never been examined. We focused on the adult neurogenesis and interneuropathy as features of neurodevelopmental disorders and investigated them with the Iqsec2 knockout mouse.
Methods : Four-month-old Iqsec2 knockout male mice were injected with bromodeoxyuridine (BrdU) to label newly born hippocampal neurons. We estimated the number of the adult-born neurons in the hippocampus by immunohistochemistry with antibodies against BrdU and NeuN, a neuronal marker. We also quantified parvalbuminpositive neurons, a dominant subtype of GABAergic interneurons by immunohistochemistry.
Results : We observed that the number of parvalbumin interneurons decreased in the medial prefrontal cortex and the dentate gyrus of the ventral part of the hippocampus. The number of the BrdU positive neurons in the dentate gyrus of the hippocampus decreased in Iqsec2 knockout mice. The reduction of BrdU positive neurons was observed both in the dorsal and ventral parts of the hippocampus.
Conclusion : A decrease in parvalbumin-positive neurons, occurred in the medial prefrontal cortex and the hippocampus, which indicates that a mechanism of IQSEC2-related disorders may involve a deficit of interneurons. Considering that adult neurogenesis seems important for cognitive brain functions, a reduction of adult-born neurons in the hippocampus may be related to some of the phenotypes of IQSEC2-related disorders, such as intellectual disability.
